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Smooth endoplasmic reticulum. Structure and functions of the endoplasmic reticulum, Golgi complex

This is a system of channels and cavities, the walls of which consist of a single layer of membrane. The structure of the membrane is similar to the plasmalemma (fluid-mosaic), however, the lipids and proteins included here are somewhat different in chemical organization. There are two types of EPS: rough (granular) and smooth (agranular).

EPS has several functions.

  1. Transport.
  2. Membrane-forming.
  3. Synthesizes protein, fats, carbohydrates and steroid hormones.
  4. Neutralizes toxic substances.
  5. Deposits calcium.

On outer surface protein synthesis occurs in the rough ER membrane.

2. On the membrane of the smooth ER there are enzymes that synthesize fats, carbohydrates and steroid hormones.

3. On the membrane of the smooth ER there are enzymes that neutralize toxic foreign substances that have entered the cell.

Rough contains on the outside of the membrane matrix big number ribosomes, which are involved in protein synthesis. The protein synthesized on the ribosome enters the ER cavity through a special channel (Fig. 7) and from there is distributed to various parts of the cytoplasm (mainly it enters the Golgi complex). This is typical for proteins that go to export. For example, for digestive enzymes synthesized in pancreatic cells.

Ribosome mRNA

Rice. 7. Endoplasmic reticulum:

A – fragments of smooth EPS; B – fragments of rough EPS. B – functioning ribosome on the rough ER.

The smooth ER membrane contains a set of enzymes that synthesize fats and simple carbohydrates, as well as steroid hormones necessary for the body. It should be especially noted that in the membrane of the smooth EPS of liver cells there is a system of enzymes that break down foreign substances (xenobiotics) that enter the cell, including medicinal compounds. The system consists of a variety of enzyme proteins (oxidizing agents, reducing agents, acetylators, etc.).

A xenobiotic or medicinal substance (DS), interacting sequentially with certain enzymes, changes its chemical structure. As a result, the final product may retain its specific activity, may become inactive, or, conversely, acquire a new property - become toxic to the body. The enzyme system located in the ER and carrying out the chemical transformation of xenobiotics (or drugs) is called biotransformation system. Currently, this system is given great importance, because the specific activity of the drug (bactericidal activity, etc.) in the body and their toxicity depend on the intensity of its work and the quantitative content of certain enzymes in it.



While studying the blood levels of the anti-tuberculosis substance isoniazid, researchers encountered an unexpected phenomenon. When taking the same dose of the drug, its concentration in the blood plasma in different individuals turned out to be different. It turned out that in people with an intensive biotransformation process, isoniazid is quickly acetylated, turning into another compound. Therefore, its content in the blood becomes significantly lower than in individuals with low acetylation intensity. It is logical to conclude that patients with rapid acetylation, for effective treatment, it is necessary to prescribe higher doses of the drug. However, another danger arises: when isoniazid is acetylated, compounds that are toxic to the liver are formed. Therefore, increasing the dose of isoniazid in fast acetylators may result in liver damage. These are the paradoxes that pharmacologists constantly encounter when studying the mechanism of action of drugs and biotransformation systems. Therefore one of important issues, which the pharmacologist must decide - to recommend for introduction into practice a drug that would not undergo rapid inactivation in the biotransformation system and, moreover, would not turn into a compound toxic to the body. It is known that of the drugs currently recommended by the Pharmaceutical Committee, almost all undergo biotransformation processes. However, none of them completely loses their specific activity and does not cause significant harm to the body. Substances such as atropine, chloramphenicol, prednisolone, norepinephrine and many others completely retain their properties, but passing through the biotransformation system, they become more soluble in water. This means that they will be eliminated from the body fairly quickly. There are substances that activate the biotransformation system, for example, phenobarbital. Thus, in experiments conducted on mice, it was found that when a large amount of this substance enters the bloodstream in liver cells, the surface of the smooth ER doubles in a few days. Stimulation of the biotransformation system is used to neutralize toxic compounds in the body. Thus, phenobarbital is used in the treatment of hemolytic disease of newborns, when stimulation of biotransformation systems helps the body cope with excess harmful substances, for example, bilirubin. By the way, after removing the harmful substance, the excess membranes of the smooth ER are destroyed with the help of lysosomes, and after 5 days the network acquires a normal volume.

Substances synthesized in EPS membranes are delivered through channels to various organelles or to places where they are needed (Fig. 8). The transport role of EPS is not limited to this; in some areas the membrane is capable of forming protrusions, which are laced and torn away from the membrane, forming a vesicle that contains all the ingredients of the network tubule. This vesicle is capable of moving and emptying its contents in a variety of places in the cell, in particular merging with the Golgi complex.

Rough XPS Elements of the cytoskeleton


Ribosome

Mitochondria

Nucleus Cell

Rice. 8. Schematic representation of the inside of the cell (not to scale).

It is necessary to note the important role of EPS in the construction of all intracellular membranes. The very first stage of such construction begins here.

EPS also plays a significant role in the exchange of calcium ions. This ion is of great importance in the regulation of cellular metabolism, changing the permeability of membrane channels, activating various connections in the cytoplasm, etc. Smooth ER is a depot of calcium ions. If necessary, calcium is released and takes part in the life of the cell. This function is most characteristic of the ER of muscles. The release of calcium ions from the EPS is a link in the complex process of muscle contraction.

It is necessary to note the close connection of the EPS with mitochondria - the energy stations of the cell. In diseases associated with energy deficiency, ribosomes are disconnected from the membrane of the rough ER. The consequences are not difficult to predict - the synthesis of proteins for export is disrupted. And since such proteins include digestive enzymes, then in diseases associated with energy deficiency, the functioning of the digestive glands will be disrupted and, as a result, one of the main functions of the body - digestive - will suffer. Based on this, the doctor’s pharmacological tactics should be developed.

Golgi complex

In the endocrine glands, for example, in the pancreas, some vesicles, separating from the EPS, become flattened, merge with other vesicles, and stack on top of each other, like pancakes in a stack, forming the Golgi complex (CG). It consists of several structural elements– tanks, bubbles and tubes (Fig. 9). All these elements are formed by a single-layer liquid mosaic type membrane. The contents of the bubbles “mature” in the tanks. The latter are detached from the complex and move in the cytosol along microtubules, fibrils and filaments. However, the main route of vesicles is movement towards the plasma membrane. Merging with it, the vesicles empty their contents with digestive enzymes into the intercellular space (Fig. 10). From it, enzymes enter the duct and flow into the intestines. The process of excretion using vesicles of CG secretion is called exocytosis.

1

Rice. 9. Section of the Golgi complex: 1 – nucleus; 2 – nucleolus; 3 – bubbles formed in the CG; 4 – KG tanks; 5 – tube.

Membrane


Rice. 10. Formation of KG(g) tanks from bubbles:

1 – core; 2 – nucleolus; 3 – bubbles formed in the QD; 4 – KG tanks; 5 – tube.

It should be noted that exocytosis in the cell is often combined with another important cellular process - the construction or renewal of the plasma membrane. Its essence is that a bubble, consisting of a single-layer liquid-mosaic membrane, approaches the membrane and bursts, simultaneously breaking the membrane. After the contents of the bubble are released, its edges merge with the edges of the gap in the membrane, and the gap is “closed.” Another path is characteristic of vesicles, from which lysosomes are subsequently formed. These vesicles, moving along the guide filaments, are distributed throughout the cytoplasm of the cell.

In practice, in the CG there is a redistribution of proteins synthesized on the ribosomes of the rough ER and delivered through the ER channels in the CG, some of them go from the CG for export, some remain for the needs of the cell (for example, concentrated in lysosomes). The process of precise distribution of proteins has a complex mechanism, and if it fails, not only digestive functions can be affected, but also all functions associated with lysosomes. Some authors have very accurately noted that the CG in a cell is a “central railway station”, where the flow of protein passengers is redistributed.

Some microtubules end blindly.

In the CG, modification of products coming from EPS is carried out:

1. Accumulation of incoming products.

2. Dehydrate them.

3. Necessary chemical restructuring (maturation).

Previously, we noted that in the CG the formation of digestive secretions and lysosomes occurs. In addition to these functions, the organelle synthesizes polysaccharides and one of the main participants in immune reactions in the body - immunoglobulins.

And finally, KG takes an active part in the construction and renewal of plasma membranes. Pouring through the plasmalemma, the vesicles are able to integrate their membrane into it. For the construction of membranes, substances are used (Fig. 11), synthesized in EPS and “ripened” on the membranes of the KG tanks.

Exocytosis and formation

Cell membranes from

Bubble membranes.


Cell nucleus

Golgi complex

Rice. 11 Scheme of the formation of a fragment of the plasma membrane from the membrane of the CG vesicle (not to scale).

KG function:

· transport (the resulting bubbles transport enzymes out or for their own use),

Forms lysosomes

· forming (immunoglobulins, complex sugars, mucoproteins, etc. are formed in CG),

· construction: a) the membrane of CG vesicles can be embedded in the plasma membrane; b) compounds synthesized in the membrane of the tanks are used for the construction of cell membranes,

· dividing (divides the cell into compartments).

Lysosomes

Lysosomes have the appearance of small round vesicles, found in all parts of the cytoplasm, from which they are separated by a single-layer liquid-mosaic membrane. The internal contents are homogeneous and consist of a large number of various substances. The most significant of them are enzymes (about 40 - 60), which break down almost all natural polymeric organic compounds that get inside lysosomes. Inside the lysosomes the pH is 4.5 - 5.0. At these values, the enzymes are in active state. If the pH is close to neutral, characteristic of the cytoplasm, these enzymes have low activity. This is one of the mechanisms for protecting cells from self-digestion if enzymes enter the cytoplasm, for example, when lysosomes rupture. On the outside of the membrane there is a large number of a wide variety of receptors that facilitate the connection of lysosomes with endocytic vesicles. It should be noted that an important property of lysosomes is targeted movement towards the object of action. When phagocytosis occurs, lysosomes move towards the phagosomes. Their movement towards destroyed organelles (for example, mitochondria) was noted. As we wrote earlier, the directed movement of lysosomes is carried out with the help of microtubules. The destruction of microtubules leads to the cessation of phagolysosome formation. The phagocyte practically loses the ability to digest pathogens in the blood (phagocytosis). This leads to severe infectious diseases.

Under certain conditions, the lysosome membrane is capable of permeating high-molecular organic substances of the hyaloplasm (for example, proteins, lipids, polysaccharides) (Fig. 12. (4.4a), where they are broken down into elementary organic compounds (amino acids, monosaccharides, fatty acids, glycerol). Then these compounds leave the lysosomes and go to the needs of the cell. In some cases, lysosomes can “capture” and then “digest” fragments of organelles (Fig. 12. (3.3a)) and damaged or obsolete cell components (membranes, inclusions) During fasting, the vital activity of cells is maintained due to the digestion of part of the cytoplasmic structures in the lysosomes and the use of final products. endogenous nutrition characteristic of many multicellular organisms.

Endocytic vesicles formed during the process of endocytosis (phagocytosis and pinocytosis) - pinocytosis vesicles (Fig. 12. (1,1a) and phagosomes (Fig. 12. (2,2a)) - also merge with the lysosome, forming a phagolysosome. Their internal contents are microorganisms, organic substances, etc. are broken down by lysosome enzymes into elemental

Microorganisms


Dissolved

Organic 2 3

Substances


Proteins, fats Lysosome Fragments

mitochondrial carbohydrates

Rice. 12. Functions of lysosomes:

1, 1a – utilization of organic substances of hyaloplasm; 2, 2a – utilization of the contents of pinocytosis vesicles; 3, 3a – utilization of the contents of phagocytic vesicles; 4, 4a – enzymatic breakdown of damaged mitochondria. 3a – phagosomes.

ny organic compounds, which, after entering the cytoplasm, become participants in cellular metabolism. Digestion of biogenic macromolecules inside lysosomes may not be completed in some cells. In this case, undigested products accumulate in the lysosome cavity. This lysosome is called a residual body. Pigment substances are also deposited there. In humans, as the body ages, the “aging pigment” - lipofuscin - accumulates in the residual bodies of brain cells, liver and muscle fibers.

If the above can be conditionally characterized as the action of lysosomes at the cell level, then the other side of the activity of these organelles manifests itself at the level of the whole organism, its systems and organs. First of all, this concerns the removal of organs that die during embryogenesis (for example, the tail of a tadpole), during the differentiation of cells of certain tissues (replacement of cartilage with bone), etc.

Considering the great importance of lysosome enzymes in the life of the cell, it can be assumed that any disruption of their work can lead to serious consequences. If the gene that controls the synthesis of any lysosome enzyme is damaged, the latter will experience a structural disorder. This will lead to the accumulation of “undigested” products in the lysosomes. If there are too many such lysosomes in a cell, the cell is damaged and, as a result, the functioning of the corresponding organs is disrupted. Hereditary diseases that develop according to this scenario are called “lysosomal storage diseases.”

Attention should also be paid to the participation of lysosomes in the formation of the immune status of the body (Figure 13). Once in the body, the antigen (for example, a toxin of a microorganism) is mainly (about 90%) destroyed, which protects cells from its damaging effects. Antigen molecules remaining in the blood are absorbed (by pinocytosis or phagocytosis) by macrophages or special cells with a developed lysosomal system

Bacterium


Antigen

Macrophage

pinositosis



Pinocytotic


Lysosome

Peptide fragments of antigen

Rice. 13. Formation of antigen peptide fragments in the macrophage

(scale not observed).

topic. The pinocytotic vesicle or phagosome with the antigen connects with the lysosome and the enzymes of the latter break down the antigen into fragments that have greater antigenic activity and less toxicity than the original microbial antigen. These fragments are brought to the surface of cells in large quantities, and a powerful activation of the body’s immune systems occurs. It is clear that the enhancement of antigenic properties (against the background of the absence of a toxic effect), as a result of lysosomal treatment, will significantly accelerate the process of development of protective immune responses to this microorganism. The process of cleavage of antigen by lysosomes into peptide fragments is called antigen processing. It should be noted that the ER and Golgi complex are directly involved in this phenomenon.

And finally, in Lately The issue of the relationship between lysosomes and microorganisms phagocytosed by the cell is widely considered. As we stated earlier, the fusion of the phagosome and lysosome leads to the digestion of microorganisms in the phagolysosome. This is the most favorable outcome. However, other relationship options are also possible. Thus, some pathogenic (disease-causing) microorganisms, when penetrating a cell inside a phagosome, release substances that block the fusion of lysosomes with the phagosome. This makes it possible for them to survive in phagosomes. However, the lifespan of cells (phagocytes) with absorbed microorganisms is short; they disintegrate, releasing phagosomes with microbes into the blood. Microorganisms released into the bloodstream can again provoke a relapse (return) of the disease. Another option is also possible, when parts of the destroyed phagocyte, including phagosomes with microbes, are again absorbed by other phagocytes, again remaining in a living state and in a new cell. The cycle can be repeated enough long time. A case of typhus is described in an elderly patient who, as a young Red Army soldier, suffered from typhus while fighting in the First Cavalry Army. In fifty seconds extra years not only the symptoms of the disease recurred - even delusional visions returned the old man to the era civil war. The thing is that typhus pathogens have the ability to block the process of joining phagosomes and lysosomes.

Function of lysosomes:

Digestive (digesting parts of the cytoplasm and microorganisms, supplies elementary organic compounds for the needs of the cell),

recycling (cleanses the cytoplasm from decayed parts),

participate in the removal of dying cells and organs,

· protective (digestion of microorganisms, participation in the body’s immune reactions).

Ribosomes.

This is the protein synthesis apparatus in the cell. The ribosome consists of two subunits - large and small. The subunits have a complex configuration (see Fig. 14) and consist of proteins and ribosomal RNA (rRNA). Ribosomal RNA serves as a kind of scaffold onto which protein molecules are attached.

The formation of ribosomes occurs in the nucleolus of the cell nucleus (this process will be discussed below). The formed large and small subunits exit through nuclear pores into the cytoplasm.

In the cytoplasm, ribosomes are in a dissociated or dispersed state, this dissociated ribosomes. In this state, they are not able to attach to the membrane. This is not the working state of the ribosome. In its working state, the ribosome is an organelle consisting of two subunits attached to each other, between which a strand of mRNA passes. Such ribosomes can “float” freely in the cytosol; they are called free ribosomes, or attach to various membranes,


A B C D

Rice. 14. Natural form of the small (A) and large (B) ribosomal subunit. Whole ribosome (B). Schematic representation of a ribosome (D)

for example to the EPS membrane. On the membrane, the ribosome is most often located not alone, but in an ensemble. There may be a different number of ribosomes in the ensemble, but they are all connected by one strand of mRNA. This makes the ribosomes work very efficiently. While the next ribosome finishes protein synthesis and leaves the mRNA, others continue this synthesis, being in different places of the RNA molecule. An ensemble of such ribosomes
called polysome(Fig. 15).

End of protein synthesis Beginning of protein synthesis

Rice. 15. Scheme of protein synthesis by a polysome.

In the picture, the polysome is made up of five different ribosomes.

Typically, proteins for export are synthesized on the membranes of the rough ER, and in the hyaloplasm - for the needs of the cell. If, during a disease, the detachment of ribosomes from membranes and their transition into the hyaloplasm is detected, then this can be considered as a protective reaction - on the one hand, cells reduce protein export and increase protein synthesis for internal needs. On the other hand, such detachment of ribosomes indicates the upcoming energy deficiency of the cell, since the attachment and retention of ribosomes on membranes requires energy, the main supplier of which in the cell is ATP. A lack of ATP naturally leads not only to the detachment of ribosomes from the membrane, but also to the inability of free ribosomes to attach to the membrane. This leads to the exclusion of the effective protein generator, the rough ER, from the molecular economy of the cell. It is believed that energy deficiency is a serious disorder of cellular metabolism, most often associated with a disruption in the activity of energy-dependent processes (for example, in mitochondria).

There are three different sites in the ribosome to which RNA binds—one for messenger RNA (mRNA, or mRNA), and two for transfer RNA. The first is located at the junction of the large and small subunits. Of the last two, one section holds the tRNA molecule and forms bonds between amino acids (peptide bonds), which is why it is called the P-center. It is located in the small subunit. And the second serves to hold the newly arrived tRNA molecule loaded with amino acid. It is called the A-center.

It should be emphasized that during protein synthesis, some antibiotics can block this process (we will dwell on this in more detail when we describe translation).

Mitochondria.

They are called the “energy stations of the cell.” In eukaryotes, a large number of electrons and protons are formed during the process of glycolysis, the Krebs cycle and other biochemical reactions. Some of them participate in various biochemical reactions, the other part accumulates in special compounds. There are several of them. The most important of them are NADH and NADPH (nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate). These compounds in the form of NAD and NADP are acceptors - a kind of “traps” of electrons and protons. After adding electrons and protons to them, they turn into NADH and NADPH and are already donors of elementary particles. "Catching" them in the most various parts cells, they transport particles to various parts of the cytoplasm and, distributing them to the needs of biochemical reactions, ensure the uninterrupted flow of metabolism. These same compounds supply electrons and protons to mitochondria from the cytoplasm and from the mitochondrial matrix, where a powerful generator of elementary particles is located - the Krebs cycle. NADH and NADPH, being integrated into the electron transport chain (see below), transfer particles to ATP synthesis. Energy is drawn from ATP for all processes occurring in the cell that require energy.

Mitochondria have two membranes of a fluid mosaic type. Between them there is an intermembrane space. The inner membrane has folds - cristae (Fig. 16). The inner surface of the cristae is dotted with mushroom-shaped bodies having a stalk and a head.

ATP synthesis occurs in mushroom bodies. In the very thickness of the inner membrane of mitochondria there are enzyme complexes that transfer electrons from NADH 2 to oxygen. These complexes are called respiratory chain or chain of transmission

Ribosome

A B C


Circular DNA

Rice. 16. Mitochondria:

A – General scheme of mitochondrial organization. B – area of ​​the crista with mushroom bodies:

1 – outer membrane of mitochondria; 2 – intermembrane matrix; 3 – internal membrane; 4 – matrix; 5 – crista; 6 – mushroom-shaped bodies.

nose of electrons. Due to movement uh ATP synthesis occurs through this complex of electrons. ATP is the main energy supplier for all cellular processes. Mitochondria are the main consumers of oxygen in the body. Therefore, mitochondria are the first to react to a lack of oxygen. This reaction is unambiguous - lack of oxygen (hypoxia) leads to swelling of mitochondria, subsequently the cells are damaged and die.

Different types of eukaryotic cells differ from each other both in the number and shape of mitochondria and in the number of cristae. The content of organelles in a cell ranges from 500 to 2000, depending on the energy requirement. So actively working cells of the intestinal epithelium contain many mitochondria, and in sperm they form a network that wraps around the flagellum, providing it with energy for movement. In tissues with high level oxidative processes, for example in the heart muscle the number of cristae is many times greater than in ordinary cells. In the mitochondria of the heart muscle their number is 3 times greater than in the mitochondria of the liver.

The life of mitochondria is measured in days (5 – 20 days in different cells). Obsolete mitochondria die, break up into fragments and are utilized by lysosomes. Instead, new ones are formed, which appear as a result of the division of existing mitochondria.

Typically, the mitochondrial matrix contains 2–10 DNA molecules. These are ring structures that encode mitochondrial proteins. Mitochondria contain the entire protein synthesis apparatus (ribosomes, mRNA, tRNA, amino acids, transcription and translation enzymes). Therefore, the processes of replication, transcription and translation are carried out in mitochondria, and mRNA maturation - processing - occurs. Based on this, mitochondria are semi-autonomous units.

An essential point in the activity of mitochondria is the synthesis of steroid hormones and some amino acids (glutamic). Obsolete mitochondria can perform a storage function - accumulate excretion products or accumulate harmful substances that have entered the cell. It is clear that in these cases the mitochondria ceases to perform its main function.

Functions of mitochondria:

accumulation of energy in the form of ATP,

· depositing,

· synthetic (synthesis of proteins, hormones, amino acids).

Cytoplasm includes the liquid contents of the cell or hyaloplasm and organelles. The plasmalemma is 80-90% water. The dense residue includes various electrolytes and organic substances. From the point of view of substance content and enzyme concentration, hyaloplasm can be divided into central and peripheral. The content of enzymes in the peripheral hyaloplasm is much higher; in addition, it has a higher concentration of ions. The hyaloplasm is compartmentalized mainly by thin filaments. Although all other components of COCA perform a structural function. Some organelles, for example, ribosomes, mitochondria, and the cell center interact with fibrillar structures, so we can say that the entire cytoplasm is structurally organized. Cell organelles are divided into membrane and non-membrane. Membranous organelles include: Golgi complex, ER, lysosomes, peroxisomes. Non-membrane organelles include: the cell center, ribosomes (in prokaryotes, only ribosomes are present among the organelles).

E.P.S.

This is a structurally unified membrane system that permeates the entire cell and which is believed to have been the first to form during the formation of the eukoryotic cell. Exocytosis of the plasmalemma occurred, and such cells received a certain advantage, because a compartment has emerged in which certain enzymatic processes can be carried out, namely the EPS cavity. From a functional point of view, the EPS can be divided into 3 sections:

    rough or granular EPS. It is represented by flattened membrane cisterns on which ribosomes are located.

    intermediate ER, also represented by flattened cisternae, but ribosomes are not located on them

    The smooth ER is represented by a network of branched anostomizing membrane tubes. There are no ribosomes on the membrane.

Functions of shEPS.

The main function is related to the synthesis and segregation of proteins. This is largely determined by the fact that special proteins ribophorins are located on the membrane, with which most ribosomes are able to interact. That. elongation and termination of protein synthesis can occur on the ER membrane. In some cases, the ribosomes on which protein synthesis occurs in the hyaloplasm do not complete it and enter the so-called translation pause; then, with the help of special mooring proteins, such ribosomes attach to the shEPS membrane and exit the translation pause, completing protein synthesis. In addition to ribophorins, a special complex of integral proteins is formed on the shEPS membrane, which is called the translocation complex. It is involved in the transport of certain proteins across the shEPS membrane into its cavity. All proteins that are synthesized on EPS ribosomes can be divided into two groups:

    proteins that go into the PAK and healoplasm

    proteins that go into the ER cavity and that have a special peptide sequence at their end; it is recognized by the receptors of the translocation complex and is separated during the passage of the protein through the translocation complex.

The first stage of sigrigation takes place on the shEPS membrane. In the cavity of the shEPS, proteins segregate into two streams:

    proteins of the EPS itself, for example, ribophorins, proteins of the translocation complex, receptors, enzymes. These proteins have a special amino acid retention signal and are called resident proteins.

    proteins that are excreted from the shEPS cavity into the intermediate EPS do not have a delay signal and are still glycosylated in the shEPS cavity. Such proteins are called transit proteins.

WITH inside on the membrane of the intermediate EPS there are receptors that recognize the hydrocarbon signal part. Due to exocytosis, membrane vesicles are formed in the intermediate EPS, which contain glycosylated proteins and receptors that recognize them. These vesicles are directed to the Golgi complex.

In addition to the synthesis and segregation of proteins, the final stages of the synthesis of some membrane lipids are carried out in shEPS.

Functions of the intermediate EPS.

It involves the budding of membrane vesicles using clathrin-like proteins. These proteins greatly increase the rate of exocytosis.

Functions of smooth EPS.

    There are enzymes on the GEPS membrane that synthesize almost all cellular lipids. This primarily applies to phospholipids and ceramide. In addition, enzymes that are involved in the synthesis of cholesterol, which in turn is a precursor of steroid hormones, are localized in the smooth ER. Cholesterol is mainly synthesized by hepatocytes, therefore hypocholesteremia is observed in various viral hepatitis. The result is anemia, because red blood cell membranes are affected. In some cells, for example, the adrenal glands and gonads, steroid hormones are synthesized, and in the adrenal glands, female sex hormones are first synthesized, and then, based on them, male sex hormones.

    calcium deposition and regulation of Ca concentration in the hyaloplasm. This function is determined by the fact that there are carriers for Ca on the membrane of the gEDS tubes, and Ca-binding proteins are located in the gEDS cavity. Due to active transport with the help of the Ca2 pump, it is pumped into the ER cavity and binds to proteins. When the Ca concentration in the cell decreases, Ca is removed into the hyaloplasm by passive transport. This function is especially developed in muscle cells, for example, in cardiomyocytes. Ca transport can be caused by activation of the phospholipase system. Regulation of calcium levels in the cell is especially important under conditions of calcium overload. With an excess of Ca, Ca-dependent apoptosis is possible. Therefore, in the membrane of the ER there is a protein that prevents apoptosis

    detoxification. Performed mainly by liver cells, which receive medications and various toxic substances from the intestines. In liver cells, toxic hydrophobic substances are converted into non-toxic hydrophobic substances using specific oxidoreductases

    smooth ER is involved in carbohydrate metabolism. This function is especially characteristic of liver cells, muscle cells, and intestinal cells. In these cells, the enzyme glucose-6-phosphatase is localized on the gED membrane, which is capable of cleaving the phosphate residue from glucose. Glucose can be released into the blood only after dephosphorylation; with hereditary defects of this enzyme, Gierke's disease is observed. This disease is characterized by the accumulation of excess glycogen in the liver and kidneys, as well as hypoglycemia. In addition, a large amount of lactic acid is formed, which leads to the development of acidosis.

GOLGI COMPLEX.

The universal function of the Golgi complex is that it is involved in:

    formation of PAK components

    formation of secretory granules

    formation of lysosomes

in the Golgi complex, segregation of proteins is observed that are transported here from the ER. (the proteins of the Golgi complex themselves are synthesized on ribosomes, which are localized in the immediate vicinity of the complex. These proteins have a signal sequence and are transported into the cavity of the Golgi complex through the translocation complex.)

Membrane bubbles coming from the EPS merge with the rescue tank. The rescue tank performs the function of returning receptors and mooring proteins to the EPS. Proteins from the salvage cistern are transported to the adjacent cis compartment cistern. Here, segregation of proteins into two streams occurs. Some proteins are phospholylated due to the special enzyme phosphoglycosidase, i.e. Phospholylation occurs on the carbohydrate part. After this, the proteins enter the medial section, where various chemical modifications occur: glycosylation, acetylation, sialylation, after which the proteins enter the trans section, where partial proteolysis of proteins is observed; further chemical modifications are possible, and then the proteins in the transdistribution section are segregated into three streams:

    a constant or constitutive flow of proteins to PAK, due to which the components of the plasmalemma and glycocalyx are regenerated

    flow of secretory granules. They can linger either near the Golgi complex or under the plasmalemma, this is the so-called inducible exocytosis

    with the help of this flow, membrane vesicles with phospholylated proteins are removed from the Golgi complex. This is a stream of so-called primary lysosomes, which then participate in the phagic cycles of the cell. In addition, in the Golgi complex the synthesis of glycosaminoglycans occurs, many glycoproteins and glycolipids are synthesized, the final synthesis of sphingolipids occurs, and condensation of dissolved substances occurs.

LYSOSOMES.

These are universal organelles of a eukaryotic cell, which is represented by membrane vesicles with a diameter of 0.4 μm, which are involved in providing the cell with hydrolysis reactions. All lysosomes have a matrix consisting of mucopolysaccharides, to which inactive hydrolases are localized. Inhibition of hydrolases is carried out due to their glycosylation in the EPS, due to phosphorylation in the Golgi complex, due to the fact that the pH of the matrix does not correspond to hydrolysis reactions. The functions of lysosomes are realized in two phagic cycles:

    autophagic cycle

    heterophagy cycle

Autophagy cycle.

With this loop you can:

    break down old cell components (mitochondria) that have lost their functional activity. This ensures physiological regeneration of the cell and the possibility of its existence much longer than any of its structures

    split spares nutrients in a cage

    break down excess secretory granules.

That. The autophagic cycle provides the cell with monomers that are necessary for the synthesis of new biopolymers inherent to the cell. In some cases, when exogenous nutrition of the cell is absent, it becomes the only source of monomers, i.e. the cell switches to exogenous nutrition. With prolonged starvation, this leads to cell lysis. There are 2 types of autophagic cycle:

    macroautophagy or typical autophagy. It begins with the formation of membrane vesicles, which enclose the old cell organelle. This vesicle is called an autophagosome. The primary lysosome, formed in the Golgi complex and containing inactive hydrolases, fuses with the autophagosome. The fusion process activates protol pumps or pumps on the membrane of the secondary lysosome. Protons are pumped into the lysosome, which leads to a shift in Ph; the enzyme acid phosphatase is activated on the membrane, which cleaves off the phosphate residue from hydrolases. Hydrolases become active and begin to cleave off complex molecules, and monomers enter the cytoplasm. Autophagasomes and primary lysosomes can fuse with the secondary lysosome until the hydrolases lose their activity and the secondary lysosomes turn into telolysosomes. Telolysosomes are either excreted from the cell or accumulate in it.

    microautophagy. In this case, the substances to be degraded enter the primary lysosome not in the form of an autophagic vesicle, but directly through the lysosome membrane. In this case, phosphorylation of certain proteins of the primary lysosome is observed.

Pathologies. The causes of pathologies may be destabilization of the membrane of the primary lysosome. There is a massive release of hydrolases into the cytoplasm and uncontrolled breakdown of cell components. Such destabilizing agents are ionizing radiation, toxins of some mushrooms, vitamins A, D, E, intense physical exercise, hyper- and hypothermia. Stress factors cause such a release of hydrolases, because It begins to act on the cells of the body by increasing the amount of adrenaline, which destabilizes the membrane. Options for superstabilization of the lysosomal membrane are possible. In this case, lysosomes cannot enter the phagic cycle. When the structure of lysosome enzymes is disrupted, various diseases are observed, which most often lead to the death of the organism. If proteins in the Golgi complex are not phospholylated, then hydrolases are found not in primary lysosomes, but in secretory streams that are removed from the cell. One of the pathologies is Y-cell disease, characteristic of fibroblasts, connective tissue cells. There, lysosomes do not contain hydrolases. They are excreted into the blood plasma. Various substances accumulate in fibroblasts, which leads to the development of storage disease (Tay-Sachs syndrome). A large amount of complex carbohydrates - glycosides - accumulates in neurons, and lysosomes occupy a very large volume. The child loses emotionality, stops smiling, stops recognizing parents, lags behind in psychomotor development, loses vision and dies by the age of 4-5. Storage diseases may be associated with pathological development of lysosomal enzymes, but usually lead to death. Variants of normal cell lysis during the autophagic cycle are possible. This mainly concerns cell lysis in different organisms during embryonic development. In humans, the membranes between the fingers undergo autolysis. The tadpole's tail undergoes autolysis. IN to the greatest extent Insects undergoing complete metamorphosis undergo autolysis.

Heterophagic cycle.

It involves the breakdown of substances entering the cell from the external environment. Due to any type of endocytosis, a heterophagosome is formed, which is capable of merging with the primary lysosome. The entire further heterophagy cycle is carried out in the same way as the autophagic one.

Functions of the heterophagic cycle.

    Trophic in unicellular organisms

    Protective. Characteristic of neutrophils and macrophages.

There are variants of the heterophagic cycle, in which hydrolases are removed from the cell into the external environment. For example, wall digestion, acrosome reaction of the sperm. The modification hetephagy cycle is observed in bone fractures; at the sites of fractures, the interfragmental gap is filled with cartilage tissue, then due to the activity of special osteoblast cells. Cartilage tissue bone is destroyed and callus is formed. Pathologies of the heterophagic cycle are various immunodeficiencies.

PEROXYSOMES.

This is a universal membrane cell organelle with a diameter of approximately 0.15-0.25 nm. The main function of peroxisomes is the breakdown of long-radical fatty acids. Although in general they can perform other functions. Peroxisomes in a cell are formed only due to the division of maternal peroxisomes, therefore, if for some reason peroxisomes do not enter the cell, then the cell dies due to the accumulation of fatty acids. The membrane of peroxisomes has a typical fluid-mosaic structure and can increase due to the transport of complex lipids and proteins by special proteins.

Functions.

    Breakdown of fatty acids. Peroxisomes contain enzymes belonging to the group of oxidoreductase enzymes, which begin the breakdown of fatty acids by eliminating acetic acid residues and form a double bond inside the fatty acid radical and hydrogen peroxide is formed as a by-product. Peroxide is broken down by a special enzyme, catalase, into H 2 O and O 2. This process of fatty acid breakdown is called β-oxidation; it occurs not only in peroxisomes, but also in mitochondria. Short radical acids are broken down in mitochondria. In any case, cleavage occurs with the formation of acetic acid or acetate residues. Acetate reacts with coenzyme A to form acetylCoA. This substance is a key metabolic product into which all organic compounds are broken down. AcCoA can be used in energy metabolism and new fatty acids are formed on the basis of AcCoA. Bowman-Zellweger syndrome occurs when β-oxidation of fatty acids is impaired. It is characterized by the absence of peroxisomes in cells. Newborns are born with very low weight and with pathological development of some internal organs, for example, brain, liver, kidneys. They are severely retarded in development, die early (before 1 year), and a large number of long-radical acids are found in the cells.

    Peroxisomes are involved in the detoxification of many harmful substances, such as alcohols, aldehydes and acids. This function is characteristic of liver cells, and peroxisomes in the liver are larger. Detoxification of poisonous substances occurs due to their oxidation. For example, the oxidation of ethanol proceeds to H 2 O and acetaldehyde. The oxidation of 50% ethanol takes place in peroxisomes. The resulting acetaldehyde enters the mitochondria, where acetylCoA is formed from it. With chronic alcohol consumption, the amount of acetylCoA in hepatocytes increases sharply. This leads to a decrease in β-oxidation of fatty acids and to the synthesis of new fatty acids. Consequently, fats begin to be synthesized, which are deposited in liver cells and this leads to fatty liver degeneration (cirrhosis)

    Peroxisomes are capable of catalyzing the oxidation of urates, because they contain the enzyme urate oxidase. However, in higher primates and humans this enzyme is inactive, so a large amount of urate circulates in the blood in dissolved form. They are well filtered in the glomeruli and excreted in secondary urine. The concentration of urates in the blood contributes to the development of certain diseases, for example, hereditary pathologies of purine metabolism lead to an increase in the concentration of urates tenfold. As a result, gout develops, which consists of the deposition of urate in the joints and some tissues, as well as the occurrence of urate stones in the kidneys.

An important function of the PAK is the function individualization. It manifests itself in the differences between cells in the chemical structure of the components of the glycocalyx. These differences may concern the structure of the supramembrane domains of several integral and semi-integral proteins. Great importance in the implementation of the individualization function there are differences in the carbohydrate components of the glycocalyx (oligosaccharides of glycolipids and PAA glycoproteins). These differences may concern the glycocalyx of identical cells of different organisms. Different compositions of the glycocalyx are also characteristic of different cells of the same multicellular organism. The molecules responsible for the individualization function are called antigens. The structure of antigens is controlled by certain genes. Each gene can determine several variants of the same antigen. The body has a large number of different antigen systems. As a result, it has a unique set of variants of different antigens. This demonstrates the individualization function of the PAK.

PAC is characterized by locomotor function. It is realized in the form of movement of individual sections of the PAC or the entire cell. This function is carried out on the basis of the submembrane musculoskeletal apparatus. With the help of mutual sliding and polymerization - depolarization of microfibrils and microtubules in certain areas of the PAA, protrusions of sections of the plasmalemma are formed. On this basis, endocytosis occurs. The coordinated movement of many sections of the PAC leads to the movement of the entire cell. Macrophages are highly mobile cells of the immune system. They are capable of phagocytosis of foreign substances and even whole cells and move throughout almost the entire body. Violation of the locomotor function of macrophages causes increased sensitivity of the body to pathogens of infectious diseases. This is due to the participation of macrophages in immune reactions.

In addition to the considered universal functions of the PAK, this cell subsystem can also perform other specialized functions.

6. Structure and functions of eps.

The endoplasmic reticulum, or endoplasmic reticulum, is a system of flat membrane cisterns and membrane tubes. Membrane tanks and tubes are interconnected and form a membrane structure with common contents. This allows you to isolate certain areas of the cytoplasm from the main nialoplasm and implement some specific cellular functions in them. As a result, functional differentiation of different zones of the cytoplasm occurs. The structure of EPS membranes corresponds to the liquid mosaic model. Morphologically, two types of EPS are distinguished: smooth (agranular) and rough (granular). Smooth ER is represented by a system of membrane tubes. Rough EPS is a membrane tank system. On the outside of the rough EPS membranes there are ribosomes. Both types of EPS are structurally dependent - membranes of one type of EPS can transform into membranes of another type.

Functions endoplasmic reticulum:

    Granular EPS is involved in protein synthesis; complex protein molecules are formed in the channels.

    Smooth ER is involved in the synthesis of lipids and carbohydrates.

    Transport of organic substances into the cell (through EPS channels).

    Divides the cell into sections, in which different chemical reactions and physiological processes can occur simultaneously.

Smooth XPS is multifunctional. Its membrane contains enzyme proteins that catalyze the reactions of membrane lipid synthesis. Some non-membrane lipids (steroid hormones) are also synthesized in the smooth ER. The composition of the membrane of this type of EPS includes Ca 2+ transporters. They transport calcium along a concentration gradient (passive transport). During passive transport, ATP is synthesized. With their help, the concentration of Ca 2+ in the hyaloplasm is regulated in the smooth ER. This parameter is important for regulating the functioning of microtubules and microfibrils. In muscle cells, smooth ER regulates muscle contraction. The EPS detoxifies many substances harmful to the cell (medicines). Smooth ER can form membrane vesicles, or microbodies. Such vesicles carry out specific oxidative reactions in isolation from the EPS.

Main function rough XPS is protein synthesis. This is determined by the presence of ribosomes on the membranes. The rough ER membrane contains special proteins ribophorins. Ribosomes interact with ribophorins and are fixed to the membrane in a certain orientation. All proteins synthesized in the EPS have a terminal signal fragment. Protein synthesis occurs on the ribosomes of the rough ER.

Post-translational modification of proteins occurs in the rough ER cisterns.

7. Golgi complex and lysosomes. Structure and functions .

The Golgi complex is a universal membrane organelle of eukaryotic cells. The structural part of the Golgi complex is represented by the system membrane tanks, forming a stack of tanks. This stack is called a dictyosome. Membranous tubes and membrane vesicles extend from them.

The structure of the membranes of the Golgi complex corresponds to a fluid-mosaic structure. Membranes of different poles are divided according to the number of glycolipids and glycoproteins. At the proximal pole, new dictyosome cisterns are formed. Small membrane vesicles break off from areas of the smooth ER and move to the proximal pole area. Here they merge and form a larger tank. As a result of this process, substances that are synthesized in the ER can be transported into the cisterns of the Golgi complex. Vesicles break off from the lateral surfaces of the distal pole and participate in enjocytosis.

The Golgi complex performs 3 general cellular functions:

    Cumulative

    Secretory

    Aggregation

Certain biochemical processes take place in the cisterns of the Golgi complex. As a result, chemical modification of the membrane components of the Golgi complex cisterns and the molecules inside these cisterns is carried out. The membranes of the cisterns of the proximal pole contain enzymes that synthesize carbohydrates (polysaccharides) and their attachment to lipids and proteins, i.e. glycosylation occurs. The presence of this or another carbohydrate component in glycosylated proteins determines their fate. Depending on this, proteins enter different areas of the cell and are secreted. Glycosylation is one of the stages of secretion maturation. In addition, proteins in the Golgi cisternae can be phosphorylated and acetylated. Free polysaccharides can be synthesized in the Golgi complex. Some of them undergo sulfation with the formation of mucopolysaccharides (glycosaminoglycans). Another option for secretion maturation is protein condensation. This process involves removing water molecules from the secretory granules, resulting in thickening of the secretion.

Also, the versatility of the Golgi complex in eukaryotic cells is its participation in the formation lysosomes

Lysosomes are membrane organelles of the cell. Inside the lysosomes there is a lysosomal matrix of mucopolysaccharides and enzyme proteins.

The lysosome membrane is a derivative of the EPS membrane, but has its own characteristics. This concerns the structure of the bilipid layer. In the lysosome membrane it is not continuous (not continuous), but includes lipid micelles. These micelles constitute up to 25% of the surface of the lysosomal membrane. This structure is called lamellar micellar. A variety of proteins are localized in the lysosome membrane. These include enzymes: hydrolases, phospholipases; and low molecular weight proteins. Hydrolases are enzymes specific to lysosomes. They catalyze reactions of hydrolysis (splitting) of high molecular weight substances.

Functions of lysosomes:

    Digestion of particles during phagocytosis and pinocytosis.

    Protective during phagocytosis

    Autophagy

    Autolysis in ontogenesis.

The main function of lysosomes is participation in heterophagotic cycles (heterophagy) and autophagic cycles (autophagy). With heterophagy, substances foreign to the cell are broken down. Autophagy is associated with the breakdown of the cell's own substances. The usual variant of heterophagy begins with endocytosis and the formation of an endocytic vesicle. In this case, the vesicle is called a heterophagosome. In another variant of heterophagy, the stage of endocytosis of foreign substances is absent. In this case, the primary lysosome is immediately involved in exocytosis. As a result, matrix hydrolases find themselves in the cell glycocalyx and are able to break down extracellular foreign substances.

Structure of the endoplasmic reticulum

Definition 1

Endoplasmic reticulum(ER, endoplasmic reticulum) is a complex ultramicroscopic, highly branched, interconnected system of membranes that more or less evenly penetrates the mass of the cytoplasm of all eukaryotic cells.

EPS is a membrane organelle consisting of flat membrane sacs - cisterns, channels and tubes. Thanks to this structure, the endoplasmic reticulum significantly increases its area inner surface cells and divides the cell into sections. It's filled inside matrix(moderately dense loose material (synthesis product)). Contents of various chemical substances in sections is not the same, therefore, in a cell, various things can happen both simultaneously and in a certain sequence chemical reactions in a small cell volume. The endoplasmic reticulum opens in perinuclear space(the cavity between two caryolem membranes).

The membrane of the endoplasmic reticulum consists of proteins and lipids (mainly phospholipids), as well as enzymes: adenosine triphosphatase and enzymes for the synthesis of membrane lipids.

There are two types of endoplasmic reticulum:

  • Smooth (agranular, aES), represented by tubes that anastomose with each other and do not have ribosomes on the surface;
  • Rough (granular, grES), also consisting of interconnected cisterns, but they are covered with ribosomes.

Note 1

Sometimes they also allocate passing or transient(tES) endoplasmic reticulum, which is located in the area of ​​​​transition of one type of ES to another.

Granular ES is characteristic of all cells (except sperm), but the degree of its development varies and depends on the specialization of the cell.

GRES of epithelial glandular cells (pancreas, producing digestive enzymes, liver, synthesizing serum albumin), fibroblasts (connective tissue cells producing collagen protein), plasma cells (producing immunoglobulins) is highly developed.

Agranular ES predominates in adrenal cells (synthesis of steroid hormones), in muscle cells (calcium metabolism), in the cells of the fundic glands of the stomach (release of chlorine ions).

Another type of EPS membranes are branched membrane tubes containing a large number of specific enzymes inside, and vesicles - small vesicles surrounded by a membrane, mainly located next to the tubes and cisterns. They ensure the transfer of those substances that are synthesized.

EPS functions

The endoplasmic reticulum is an apparatus for the synthesis and, partly, transport of cytoplasmic substances, thanks to which the cell performs complex functions.

Note 2

The functions of both types of EPS are associated with the synthesis and transport of substances. The endoplasmic reticulum is a universal transport system.

The smooth and rough endoplasmic reticulum with its membranes and contents (matrix) perform common functions:

  • separation (structuring), due to which the cytoplasm is distributed in an orderly manner and does not mix, and also prevents random substances from entering the organelle;
  • transmembrane transport, due to which necessary substances are transferred through the membrane wall;
  • synthesis of membrane lipids with the participation of enzymes contained in the membrane itself and ensuring the reproduction of the endoplasmic reticulum;
  • Due to the potential difference that arises between the two surfaces of the ES membranes, it is possible to ensure the conduction of excitation impulses.

In addition, each type of network has its own specific functions.

Functions of smooth (agranular) endoplasmic reticulum

The agranular endoplasmic reticulum, in addition to the named functions common to both types of ES, also performs functions unique to it:

  • calcium depot. In many cells (in skeletal muscles, in the heart, eggs, neurons) there are mechanisms that can change the concentration of calcium ions. Striated muscle tissue contains a specialized endoplasmic reticulum called the sarcoplasmic reticulum. This is a reservoir of calcium ions, and the membranes of this network contain powerful calcium pumps that can release large amounts of calcium into the cytoplasm or transport it into the cavities of the network channels in hundredths of a second;
  • lipid synthesis, substances such as cholesterol and steroid hormones. Steroid hormones are synthesized mainly in the endocrine cells of the gonads and adrenal glands, in the cells of the kidneys and liver. Intestinal cells synthesize lipids, which are excreted into the lymph and then into the blood;

    • detoxification function– neutralization of exogenous and endogenous toxins;

    Example 1

    Kidney cells (hepatocytes) contain oxidase enzymes that can destroy phenobarbital.

    organelle enzymes take part in glycogen synthesis(in liver cells).

Functions of the rough (granular) endoplasmic reticulum

In addition to the listed general functions, the granular endoplasmic reticulum is also characterized by special ones:

  • protein synthesis at the State Power Plant has some peculiarities. It begins on free polysomes, which subsequently bind to ES membranes.
  • The granular endoplasmic reticulum synthesizes: all proteins of the cell membrane (except for some hydrophobic proteins, proteins of the internal membranes of mitochondria and chloroplasts), specific proteins of the internal phase of membrane organelles, as well as secretory proteins that are transported throughout the cell and enter the extracellular space.
  • post-translational modification of proteins: hydroxylation, sulfation, phosphorylation. An important process is glycosylation, which occurs under the action of the membrane-bound enzyme glycosyltransferase. Glycosylation occurs before the secretion or transport of substances to certain parts of the cell (Golgi complex, lysosomes or plasmalemma).
  • transport of substances along the intramembrane part of the network. Synthesized proteins move through the gaps of the ES to the Golgi complex, which removes substances from the cell.
  • due to the participation of the granular endoplasmic reticulum The Golgi complex is formed.

The functions of the granular endoplasmic reticulum are associated with the transport of proteins that are synthesized in ribosomes and located on its surface. Synthesized proteins enter the EPS, fold and acquire a tertiary structure.

The protein that is transported to the cisterns changes significantly along the way. It can, for example, be phosphorylated or converted into a glycoprotein. The usual route for a protein is through the granular ER into the Golgi apparatus, from where it either exits the cell, goes to other organelles of the same cell, such as lysosomes), or is deposited as storage granules.

In liver cells, both granular and non-granular endoplasmic reticulum take part in the processes of detoxification of toxic substances, which are then removed from the cell.

Same as external plasma membrane, the endoplasmic reticulum has selective permeability, as a result of which the concentration of substances inside and outside the reticulum channels is not the same. This has implications for cell function.

Example 2

There are more calcium ions in the endoplasmic reticulum of muscle cells than in its cytoplasm. Leaving the channels of the endoplasmic reticulum, calcium ions trigger the process of contraction of muscle fibers.

Formation of the endoplasmic reticulum

The lipid components of the endoplasmic reticulum membranes are synthesized by enzymes of the reticulum itself, while the protein components come from ribosomes located on its membranes. The smooth (agranular) endoplasmic reticulum does not have its own protein synthesis factors, therefore it is believed that this organelle is formed as a result of the loss of ribosomes by the granular endoplasmic reticulum.