Golgi complex It is a stack of membrane sacs (cisterns) and an associated system of bubbles.
On the outer, concave side there is a stack of bubbles budding from the smooth. EPS, new tanks are constantly being formed, and on inside the tanks turn back into bubbles.
The main function of the Golgi complex is the transport of substances into the cytoplasm and extracellular environment, as well as the synthesis of fats and carbohydrates. The Golgi complex is involved in growth and renewal plasma membrane and in the formation of lysosomes.
The Golgi complex was discovered in 1898 by C. Golgi. Having extremely primitive equipment and a limited set of reagents, he made a discovery, thanks to which, together with Ramon y Cajal, he received Nobel Prize. He processed nerve cells dichromate solution, after which silver and osmium nitrates were added. By precipitation of osmium or silver salts with cellular structures Golgi discovered a dark-colored network in neurons, which he called the internal reticular apparatus. When painting general methods the lamellar complex does not accumulate dyes, so the zone of its concentration is visible as a light area. For example, near the nucleus of a plasma cell, a light zone is visible, corresponding to the area where the organelle is located.
Most often, the Golgi complex is adjacent to the nucleus. With light microscopy, it can be distributed in the form of complex networks or individual diffusely located areas (dictyosomes). The shape and position of the organelle are not of fundamental importance and can vary depending on the functional state of the cell.
The Golgi complex is the site of condensation and accumulation of secretion products produced in other parts of the cell, mainly in the ER. During protein synthesis, radiolabeled amino acids accumulate in gr. ER, and then they are found in the Golgi complex, secretory inclusions or lysosomes. This phenomenon makes it possible to determine the significance of the Golgi complex in synthetic processes in the cell.
At electron microscopy It can be seen that the Golgi complex consists of clusters of flat cisterns called dictyosomes. The tanks are closely adjacent to each other at a distance of 20...25 nm. The lumen of the cisterns in the central part is about 25 nm, and at the periphery expansions are formed - ampoules, the width of which is not constant. Each stack contains about 5...10 tanks. In addition to densely located flat cisterns, in the area of the Golgi complex there are a large number of small vesicles (vesicles), especially at the edges of the organelle. Sometimes they become detached from the ampoules.
On the side adjacent to the ER and the nucleus, the Golgi complex has a zone containing a significant number of small vesicles and small cisterns.
The Golgi complex is polarized, that is, qualitatively heterogeneous from different sides. It has an immature cis surface, lying closer to the nucleus, and a mature trans surface, facing the cell surface. Accordingly, the organelle consists of several interconnected compartments that perform specific functions.
The cis compartment usually faces the cell center. Its outer surface has a convex shape. Microvesicles (transport pinocytosis vesicles) coming from the EPS merge with the cisterns. Membranes are constantly renewed due to vesicles and, in turn, replenish the contents of membrane formations in other compartments. Post-translational processing of proteins begins in the compartment and continues in subsequent parts of the complex.
The intermediate compartment carries out glycosylation, phosphorylation, carboxylation, and sulfation of biopolymer protein complexes. The so-called post-translational modification of polypeptide chains occurs. Synthesis of glycolipids and lipoproteins is underway. In the intermediate compartment, as in the cis-compartment, tertiary and quaternary protein complexes. Some proteins undergo partial proteolysis (destruction), which is accompanied by their transformation necessary for maturation. Thus, the cis and intermediate compartments are required for the maturation of proteins and other complex biopolymeric compounds.
The trans compartment is located closer to the cell periphery. External surface its usually concave. The trans-compartment partially transforms into the trans-network - a system of vesicles, vacuoles and tubules.
In cells, individual dictyosomes can be connected to each other by a system of vesicles and cisternae adjacent to distal end accumulations of flat bags, so that a loose three-dimensional network is formed - a trans-network.
In the structures of the trans compartment and trans network, the sorting of proteins and other substances, the formation of secretory granules, precursors of primary lysosomes and spontaneous secretion vesicles occur. Secretory vesicles and prelysosomes are surrounded by proteins called clathrins.
Clathrins are deposited on the membrane of the forming vesicle, gradually splitting it off from the distal cistern of the complex. Bordered vesicles extend from the trans-network, their movement is hormone-dependent and controlled functional state cells. The transport process of bordered vesicles is influenced by microtubules. Protein (clathrin) complexes around the vesicles disintegrate after the vesicle is detached from the trans-network and form again at the moment of secretion. At the moment of secretion, protein complexes of vesicles interact with microtubule proteins, and the vesicle is transported to outer membrane. Spontaneous secretion vesicles are not surrounded by clathrins; their formation occurs continuously and, heading towards the cell membrane, they merge with it, ensuring the restoration of the cytolemma.
In general, the Golgi complex is involved in segregation - this is separation, separation certain parts from the bulk, and the accumulation of products synthesized in EPS, in their chemical rearrangements and maturation. In the tanks, polysaccharides are synthesized and combined with proteins, which leads to the formation of complex complexes of peptidoglycans (glycoproteins). With the help of elements of the Golgi complex, ready-made secretions are removed outside the secretory cell.
Small transport bubbles split off from the gr. EPS in ribosome-free zones. The vesicles restore the membranes of the Golgi complex and deliver polymer complexes synthesized in the ER. The vesicles are transported to the cis compartment, where they fuse with its membranes. Consequently, new portions of membranes and products synthesized in the group enter the Golgi complex. EPS.
In the cisterns of the Golgi complex, secondary changes occur in proteins synthesized in the group. EPS. These changes are associated with the rearrangement of oligosaccharide chains of glycoproteins. Inside the cavities of the Golgi complex, lysosomal proteins and secretion proteins are modified with the help of transglucosidases: oligosaccharide chains are successively replaced and extended. Modifying proteins move from the cis-compartment cisternae to the trans-compartment cisternae due to transport in vesicles containing the protein.
In the trans-compartment, proteins are sorted: on the inner surfaces of the cisternae membranes there are protein receptors that recognize secretory proteins, membrane proteins and lysosomes (hydrolases). As a result, three types of small vacuoles are split off from the distal trans-sections of dictyosomes: prelysosomes containing hydrolases; with secretory inclusions, vacuoles that replenish the cell membrane.
The secretory function of the Golgi complex is that the exported protein synthesized on ribosomes, separated and accumulated inside the ER cisterns, is transported to the vacuoles of the lamellar apparatus. The accumulated protein may then condense to form secretory protein granules (in the pancreas, mammary glands, and other glands) or remain dissolved (immunoglobulins in plasma cells). Vesicles containing these proteins are split off from the ampullary extensions of the cisterns of the Golgi complex. Such vesicles can merge with each other and increase in size, forming secretory granules.
After this, the secretory granules begin to move to the cell surface, come into contact with the plasmalemma, with which their own membranes merge, and the contents of the granules appear outside the cell. Morphologically, this process is called extrusion, or excretion (throwing out, exocytosis) and resembles endocytosis, only with the reverse sequence of stages.
The Golgi complex can sharply increase in size in cells that actively carry out secretory function, which is usually accompanied by the development of the ER, and in the case of protein synthesis - the nucleolus.
During cell division, the Golgi complex breaks down into individual cisterns (dictyosomes) and/or vesicles, which are distributed between the two dividing cells and, at the end of telophase, restore the structural integrity of the organelle. Outside of division, the membrane apparatus is continuously renewed due to vesicles migrating from the EPS and distal cisternae of the dictyosome at the expense of the proximal compartments.
The Golgi complex was discovered by Camillo Golgi in 1898. This structure is present in the cytoplasm of almost all eukaryotic (components higher organisms) cells, especially secretory cells in animals.
Golgi complex. Structure.
The structure is represented by a stack of flattened membrane sacs. They are called tanks. This stack of sacs is connected to the Golgi system). At one end of the stacks of sacs, new cisternae are constantly being formed by the fusion of vesicles that bud from the endoplasmic reticulum (a network of cavities). At the other end of the stack on the inside of the tank, they complete maturation and break up again into bubbles. This is how the tanks in the hill gradually move towards the inner side from the outer side.
In the cisterns of the structure, the maturation of proteins intended for secretion, transmembrane proteins, lysosome proteins, and others occurs. Maturing substances move sequentially through the organelle cisterns. The final folding of proteins and their modifications - phosphorylation and glycosylation - occur in them.
Characterized by the presence of a number of individual dictyosomes (stacks). There are often several stacks connected by tubes or one large stack.
Contains four main sections: trans-Golgi network, cis-Golgi, trans-Golgi and medial-Golgi. An intermediate compartment (separate region) is also attached to the structure. It is represented by a cluster of membrane vesicles in the space between the reitculum and the cis-Golgi.
The entire apparatus is a very polymorphic (diverse) organelle. Even at different stages of development of one cell, the Golgi complex can look different.
The device also differs in its asymmetry. Located closer to cell nucleus cisternae (cis-Golgi) contain the most immature proteins. These tanks are joined by continuous membrane vesicles - vesicles. Different tanks contain different resident enzymes (catalytic), which suggests that they occur sequentially with maturing proteins different processes.
Golgi complex. Functions.
The tasks of the structure include chemical modification and transport of substances entering it. Proteins that penetrate into the apparatus from the endoplasmic reticulum are the initial substrate for enzymes. After being concentrated and modified, the enzymes in the vesicles are transported to the designated site. For example, this could be the area where a new kidney is forming. With the participation of cytoplasmic microtubules, the transfer process is most active.
The Golgi complex also performs the task of attaching carbohydrate groups to proteins and the subsequent use of these proteins in the construction of the membrane of lysosomes and cells.
In some algae, cellulose fibers are synthesized in the structure of the apparatus.
The functions of the Golgi complex are quite diverse. Among them are:
- Sorting, removal, accumulation of secretory products.
- Accumulation of lipid molecules and formation of lipoproteins.
- Completion of protein modification (post-translational), namely glycosylation, sulfation, etc.
- Formation of lysosomes.
- Participation in the formation of acrosomes.
- Polysaccharide synthesis for the formation of waxes, glycoproteins, mucus, gum, matrix substances in plants (pectins, hemicellulose and others).
- Formation of contractile vacuoles in protozoa.
- Formation of the cell plate in plant cells after nuclear fission.
Golgi apparatus
The endoplasmic reticulum, plasma membrane and Golgi apparatus constitute a single membrane system of the cell, within which processes of protein and lipid exchange occur using directed and regulated intracellular membrane transport.
Each of membrane organelles characterized by a unique composition of proteins and lipids.
AG structure
AG consists of a group of flat membrane bags - tanks, collected in piles - dictyosomes(~5-10 cisternae, in lower eukaryotes >30). The number of dictyosomes in different cells ranges from 1 to ~500.
The individual cisternae of the dictyosome are of variable thickness - in the center of its membrane they are close together - the lumen is 25 nm, expansions are formed at the periphery - ampoules whose width is not constant. From the ampoules, ~50 nm-1 µm bubbles emerge, connected to the cisterns by a network of tubes.
U multicellular organisms AG consists of stacks of tanks interconnected into a single membrane system. AG is a hemisphere, the base of which faces the core. Yeast AG is represented by isolated single tanks surrounded by small vesicles, a tubular network, secretory vesicles and granules. The yeast Sec7 and Sec14 mutants display a structure reminiscent of a stacked cisternae of mammalian cells.
AG is characterized by the polarity of its structures. Each stack has two poles: proximal pole(forming, cis-surface) and distal(mature,
trans-surface). Cis pole– the side of the membrane with which bubbles merge. Trans-pole– the side of the membrane from which the vesicles bud.
Five functional compartments of AG:
1. Intermediate vesicular-tubular structures (VTC or ERGIC - ER-Golgi intermediate compartment)
2. Cis-tank (cis) - tanks located closer to the ER:
3. Medial tanks - central tanks
4. Trans tank (trans) - the tanks most distant from the ER.
5. Tubular network adjacent to the transcistern - trans-Golgi network (TGN)
The cisternae stacks are curved so that the concave transsurface faces the core.
On average, there are 3-8 cisterns in AG; there may be more in actively secreting cells (up to 13 in exocrine pancreatic cells).
Each tank has cis and trans surfaces. Synthesized proteins, membrane lipids, glycosylated in the ER, enter the AG through the cis pole. Substances are transferred through the stacks by transport
bubbles separating from the ampoules. As proteins or lipids pass through the Golgi stacks, they undergo a series of post-translational modifications, including changes to N-linked oligosaccharides:
cis: Mannosidase I trims long mannose chains to M-5
intermediate: N-acetylglucoamine transferase I transfers N-acetylglucosamine
trance: terminal sugars are added - galactose residues and sialic acid.
Structure of the Golgi Apparatus and transport scheme.
Five components of AG and transport scheme: intermediate (ERGIC), cis, intermediate, trans and trans Golgi network (TGN). 1. Entry of synthesized proteins, membrane glycoproteins and lysosomal enzymes into the transitional ER tank adjacent to the AG and 2 - their exit from the ER in vesicles bordered by COPI (anterograde transport). 3 - possible transport of cargo from tubulo-vesicular
clusters to the cis-cistern of AG in COPI vesicles; 3* - transport of cargo from earlier to later tanks; 4 - possible retrograde vesicular transport of cargo between AG tanks; 5 - return of resident proteins from AG to tER using vesicles bordered by COPI (retrograde transport); 6 and 6* - transfer of lysosomal enzymes using clathrin-lined vesicles, respectively, into early EE and late LE endosomes; 7 - regulated secretion secretory granules; 8 - constitutive integration of membrane proteins into the apical plasma membrane of the PM; 9 - receptor-mediated endocytosis using clathrin-lined vesicles; 10 return of a number of receptors from early endosomes to the plasma membrane; 11 - transport of ligands from EE to LE and Lysosomes; 12 - transport of ligands in non-clathrin vesicles.
AG functions
1. Transport- three groups of proteins pass through the AG: proteins of the periplasmic membrane, proteins intended
for export from the cell, and lysosomal enzymes.
2. Sorting for transport: sorting for further transport to organelles, PM, endosomes, secretory vesicles occurs in the trans-Golgi complex.
3. Secretion- secretion of products synthesized in the cell.
3. Glycosylation proteins and lipids: glycosidases remove sugar residues - deglycosylation, glycosyltransferases attach sugars back to the main carbohydrate chain - glycosylation. It involves glycosylation of oligosaccharide chains of proteins and lipids, sulfation of a number of sugars and tyrosine residues of proteins, as well as activation of precursors of polypeptide hormones and neuropeptides.
4. Synthesis of polysaccharides- many polysaccharides are formed in AG, including pectin and hemicellulose, which form the cell walls of plants and most glycosaminoglycans forming the intercellular matrix in animals
5. Sulfation- most sugars added to the protein core of a proteoglycan are sulfated
6. Addition of Mannose 6-Phosphate: M-6-P is added as a signal to enzymes destined for lysosomes.
GLYCOSYLATION
Most proteins begin to be glycosylated in the rough ER by the addition of N-linked oligosaccharides to the growing polypeptide chain. If the glycoprotein is folded in the desired conformation, it leaves the ER and goes to the AG, where its post-translational modification occurs.
Enzymes - glycosyltransferases - take part in the glycosylation of secreted products. They are involved in the remodeling of T-linked oligosaccharide side chains and the addition of O-linked glycans and oligosaccharide parts of glycolipid proteoglycans. The α-mannosidase enzymes I and II, which are also resident AG proteins, participate in the modification of oligosaccharides.
In addition, glycosylation of lipid-protein membrane domains called rafts occurs in AG.
Dolichol phosphate adds a carbohydrate complex - 2GlcNAc-9-mannose-3-glucose to the asparagine of the growing polypeptide. Terminal glucose is cleaved in two stages: glucosidase I cleaves off the terminal glucose residue, glucosidase II removes two more glucose residues. Then mannose is split off. At this point, the initial stage of carbohydrate processing in the ER is completed and proteins carrying the oligosaccharide complex enter the AG
In the first AG tanks, three more mannose residues are removed. At this stage, the core complex has 5 more mannose residues. N-acetylglucosamine transferase I adds one N-acetylglucosamine residue GlcNAc. Three more mannose residues are cleaved from the resulting complex. Now consists of two molecules GlcNAc-3-mannose-1-GlcNAc is a core structure to which other glycosyltransferases add
carbohydrates. Each glycosyltransferase recognizes the developing carbohydrate structure and adds its own saccharide to the chain.
SECRETION
Secretion pattern:
Proteins synthesized in the ER are concentrated at the exit sites of the transitional ER due to the activity of the coatomeric complex COPII and accompanying components and are transported to the ERGIC compartment intermediate between the ER and AG, from which they pass to the AG in budding vesicles or along tubular structures. Proteins are covalently modified as they pass through the AG cisterns and are sorted on the trans surface of the AG and sent to their destinations. Secretion of proteins requires the passive incorporation of new membrane components into the plasma membrane. To restore membrane balance, constitutive receptor-mediated endocytosis is used.
Endo and exocytotic membrane transport pathways have general patterns in the direction of movement of membrane carriers to the corresponding
targets and in the specificity of fusion and budding. The main meeting point of these paths is the AG.
Laboratory-practical lesson No. 9
Topic: “Golgi apparatus (complex)”
Purpose of the lesson : identify the morpho-functional features of the Golgi complex.
Issues for discussion
1 . Fine structure of the Golgi apparatus.
Demonstration preparations
Equipment
1. Photographs, diagrams, drawings fromAtlas on cell biology, J.-C.Roland, A. Seloshi, D. Seloshi, trans.V.P. Bely, ed. Yu.S. Chentsova. ─ M.: Mir. 1978. ─ 119 p.
Theoretical background to prepare for class
The Golgi apparatus (complex) is a membrane structure of a eukaryotic cell, an organelle primarily intended for the removal of substances synthesized in the endoplasmic reticulum. The Golgi apparatus was named after the Italian scientist Camillo Golgi, who first discovered it in 1897 (Fabene P.F., Bentivoglio M., 1998).
Rice. 1. Scheme of the Golgi Apparatus (A). Structure of the Golgi Apparatus (B)
Note: Golgi apparatus ─ cavities (cisterns) surrounded by membranes and an associated system of vesicles. Functions ─ accumulation of organic substances; “packaging” of organic substances; removal of organic substances; formation of lysosomes.
Apparatus(complex) Golgi is a stack of disc-shaped membrane sacs (cisterns), somewhat expanded closer to the edges, and an associated system of Golgi vesicles. A number of individual stacks are found in plant cells ( dictyosomes), animal cells often contain one large or several stacks connected by tubes.
In the Golgi Complex, there are 3 sections of cisterns surrounded by membrane vesicles:
1. Cis section (closest to the nucleus).
2. Medial department.
3. Trans department (furthest from the core).
These sections differ from each other in the set of enzymes. In the cis-compartment, the first tank is called the “rescue tank”, since with its help the receptors coming from the intermediate endoplasmic reticulum are returned back. Enzyme of the cis department: phosphoglycosidase (adds phosphate to the carbohydrate ─ mannose).
In the medial section there are 2 enzymes: mannazidase (cleaves off mannase) and N-acetylglucosamine transferase (adds certain carbohydrates ─ glycosamines).
In the trans section there are enzymes: peptidase (carries out proteolysis) and transferase (carries out the transfer of chemical groups).
Fine structure of the Golgi apparatus (AG). An electron microscope shows that the Golgi apparatus is represented by membrane structures collected together in a small zone (Fig. 1, 2); Flat membrane bags (tanks) are arranged in a stack; the number of such bags in a stack usually does not exceed 5-10. Between which there are thin layers of hyaloplasm. Each individual tank has a diameter of about 1 μm and variable thickness; in the center the membranes can be close together (25 nm), and at the periphery they can have expansions ─ ampoules, the width of which is not constant.
Rice. 2. Scheme of the structure of a dictyosome(according to Chentsov Yu.S., 2010)
Note : P─ proximal (cis-) part; D─ distal (trans-) part; IN─ vacuoles; C─ flat membrane tanks; A─ ampullary extensions of tanks.
In some single-celled organisms their number can reach 20. In addition to densely located flat cisterns, many vacuoles are observed in the AG zone. Small vacuoles are found mainly in the peripheral areas of the AG zone; sometimes you can see how they are laced from the ampullary extensions at the edges of the flat cisterns. It is customary to distinguish in the dictyosome zone the proximal or developing, cis-section, and the distal or mature, trans-section (Fig. 15.5). Between them is the middle or intermediate section of the AG. During cell division reticulate forms of AG disintegrate into dictyosomes who are passive
and are randomly distributed among daughter cells. As cells grow, the total number of dictyosomes increases.
Rice. 3. Types of Golgi apparatus(according to Chentsov Yu.S., 2010)
Note : A ─ reticular in intestinal epithelial cells;b─ diffuse in the cells of the spinal ganglion;I─ core;2 ─ AG;3 ─ nucleolus.
AG is usually polarized in secreting cells: its proximal part faces the cytoplasm and nucleus, and the distal part ─ to the cell surface. In the proximal area, the stacks of closely spaced cisterns are adjacent to a zone of small smooth vesicles and short membrane cisterns.
Rice. 4. Golgi apparatus (AG) in electronic microscope(according to Chentsov Yu.S., 2010)
Rice. 5. Schematic representation of the components of the Golgi apparatus(according to Chentsov Yu.S., 2010)
Note : 1 ─ EPR-AG (ERGIC) ─ intermediate zone;2 ─ cis-zone, proximal area; 3─ medial─ middle section; 4─ trans-distal area; 5─ AG trans-network.
In the middle part dictyosomes the periphery of each tank is also accompanied by a mass of small vacuoles about 50 nm in diameter.
In the distal or trans-section of dictyosomes, the last membranous flat tank is adjacent to a section consisting of tubular elements and a mass of small vacuoles, often having fibrillar pubescence along the surface from the cytoplasm ─ these are pubescent or bordered vesicles of the same type as the bordered vesicles during pinocytosis ( from ancient Greek πίνω ─ drink, absorb and κύτος ─ container, cell ─ capture by the cell surface of liquid with the substances contained in it; the process of absorption and intracellular destruction of macromolecules).
This is the so-called trans-Golgi network (TGN), where the separation and sorting of secreted products occurs. Even more distal is a group of larger vacuoles ─ this is the product of the fusion of small vacuoles and the formation of secretory vacuoles.
When studying thick sections of cells using a megavolt electron microscope, it was found that in cells individual dictosomes can be connected to each other by a system of vacuoles and cisterns. So a loose three-dimensional network is formed, which is visible in a light microscope. In the case of the diffuse form of AG, each individual section is represented by a dictyosome. In animal cells, centrioles are often associated with the membrane zone of the Golgi apparatus; Between the bundles of microtubules extending radially from them lie groups of stacks of membranes and vacuoles, which concentrically surround the cell center. This connection likely reflects the involvement of microtubules in vacuole movement.
Functions Golgi apparatus Along with proteins, membrane lipids are transported in the Golgi apparatus.
1. Separation of proteins into 3 streams:
● Cis section (closest to the nucleus); lysosomal ─ glycosylated proteins (with mannose) enter the cis-compartment of the Golgi complex, some of them are phosphorylated, and a marker of lysosomal enzymes is formed ─ mannose-6-phosphate. In the future, these phosphorylated proteins will not undergo modification, but will enter the lysosomes.
● Medial department; constitutive exocytosis (constitutive secretion). This flow includes proteins and lipids, which become components of the cell surface apparatus, including the glycocalyx, or they may be part of the extracellular matrix.
● Trans department (furthest from the core); inducible secretion ─ proteins that function outside the cell, the surface apparatus of the cell, and in the internal environment of the body enter here. Characteristic of secretory cells.
2. Formation of mucous secretions (secretory function of the Golgi apparatus) ─ glycosaminoglycans(mucopolysaccharides).
● Membrane elements AG participate in the segregation and accumulation of products synthesized in the ER, participate in their chemical rearrangements, maturation (rearrangement of oligosaccharide components of glycoproteins as part of water-soluble secretions or as part of membranes), (Fig. 6).
● In AG tanks polysaccharides are synthesized and interact with proteins, leading to the formation of mucoproteins.
●The main thing is that with the help of elements of the Golgi apparatus, the process of removing ready-made secretions outside the cell occurs. In addition, AG is a source of cellular lysosomes.
●The participation of AG in the processes of excretion of secretory products has been very well studied using the example of exocrine pancreatic cells. These cells are characterized by the presence of a large number of secretory granules ( zymogen granules), which are membrane vesicles filled with protein content. The proteins of zymogen granules include various enzymes: proteases, lipases, carbohydrates, nucleases.
During secretion, the contents of these zymogen granules are released from the cells into the lumen of the gland, and then flows into the intestinal cavity. Since the main product excreted by pancreatic cells is protein, the sequence of incorporation of radioactive amino acids into different parts of the cell was studied (Fig. 7).
Rice. 6. Diagram of the connection between the ER and the Golgi apparatus with the formation and release of zymogen from pancreatic acinar cells (according to Chentsov Yu.S., 2010)
Note : 1 ─ transition zone between EPR and AG; 2─ zone of maturation of secretory granules;3 ─ zymogen granules separated from AG; 4─ their exit (exocytosis) outside the cell.
Rice. 7. Detection sequence}
