Myelin

Myelin is a unique formation, the organization of which allows you to conduct an electrical impulse along the nerve fiber with minimal energy expenditure. Myelin sheath is a highly organized multilayer structure consisting of highly stretched and modified plasmatic membranes of Schwann's (in PNS) and oligodendroglial (in the central nervous system) cells.

The water content in myelin is about 40%. A distinctive feature of myelin compared to other cells is that it contains on average 70% lipids and 30% protein (based on dry weight). Most biological membranes have a higher ratio of proteins to lipids.

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Myelin CNS lipids

All lipids found in the brain of the rat are present in myelin, ie, there are no lipids localized exclusively in the non-myelin structures (with the exception of the specific mitochondrial lipid diphosphatidylglycerol). The converse is also true: there are no such myelin lipids that would not have been found in other subcellular fractions of the brain.

Cerebroside is the most typical component of myelin. With the exception of the earliest period of the development of the body, the concentration of cerebroside in the brain is directly proportional to the amount of myelin in it. Only 1/5 of the total galactolipid content in myelin occurs in sulfated form. Cerebrosides and sulfatides play an important role in the stability of myelin.

Myelin is also characterized by a high level of its main lipids - cholesterol, common galactolipids and ethanolamine-containing plasmalogen. It was found that up to 70% of the brain's cholesterol is in the myelin. Since almost half of the white matter of the brain can consist of myelin, it is obvious that the brain contains the greatest amount of cholesterol compared to other organs. High concentration of cholesterol in the brain, especially in myelin, is determined by the main function of neuronal tissue - to generate and conduct nerve impulses. The high content of cholesterol in myelin and the peculiarity of its structure lead to a decrease in ion leakage through the neuron membrane (due to its high resistance).

Phosphatidylcholine is also an essential part of myelin, although sphingomyelin is contained in a relatively small amount.

The lipid composition of both gray matter and white matter of the brain is clearly different from that of myelin. The composition of myelin of the brain of all studied mammalian species is almost the same; there are only minor differences (for example, rat myelin has less sphingomyelin than myelin bull or human). There are some variations, depending on the location of myelin, for example myelin isolated from the spinal cord, has a higher value of the lipid to protein ratio than myelin from the brain.

Myelin also contains polyphosphatidylinositols, of which triphosphoinositide is 4 to 6% of total myelin phosphorus, and diphosphoinositide is from 1 to 1.5%. Minor components of myelin include at least three esters of cerebroside and two lipids based on glycerol; Myelin also contains some long-chain alkanes. Myelin of mammals contains from 0.1 to 0.3% of gangliosides. Myelin contains more monosialoganglioside in M1 compared to what is found in the membranes of the brain. Myelin of many organisms, including humans, contains a unique ganglioside of sialozilgalactosylceramide OM4.

Lipid myelin PNS

Myelin lipids of the peripheral and central nervous system are qualitatively similar, but there are quantitative differences between them. Myelin PNS contains less cerebrosides and sulfatides and significantly more sphingomyelin than myelin CNS. It is interesting to note the presence of ganglioside OMP characteristic of myelin PTS of some organisms. Differences in the composition of myelin lipids of the central and peripheral nervous system are not as significant as their differences in protein composition.

Myelin proteins of the central nervous system

The protein composition of the myelin of the central nervous system is simpler than that of other brain membranes, and is mainly represented by proteolipids and basic proteins, which constitute 60-80% of the total. Glycoproteins are present in much smaller quantities. Myelin central nervous system contains unique proteins.

For myelin, the human CNS is characterized by the quantitative prevalence of two proteins: a positively charged cationic myelin protein (MBP) and myelin proteolipid protein (PLP). These proteins are the main constituents of the myelin of the central nervous system of all mammals.

Myelin proteolipid PLP (proteolipid protein), also known as the Folca protein, has the ability to dissolve in organic solvents. The molecular weight of the PLP is approximately 30 kD (Da-Dalton). Its amino acid sequence is extremely conservative, the molecule forms several domains. The PLP molecule includes three fatty acids, usually palmitic, oleic and stearic, linked to amino acid radicals by ether bond.

Myelin CNS contains somewhat lesser amounts of another proteolipid - DM-20, named after its molecular weight (20 kDa). Both DNA analysis and clarification of the primary structure showed that DM-20 is formed by the cleavage of 35 amino acid residues from the PLP protein. During development, the DM-20 appears earlier than PLP (in some cases even before the appearance of myelin); suggest that in addition to the structural role in the formation of myelin, it can participate in the differentiation of oligodendrocytes.

Contrary to the notion that PLP is necessary for the formation of compact multilamellar myelin, the process of myelin formation in mice knocked out by PLP / DM-20 occurs with only minor deviations. However, in such mice, life expectancy is reduced and overall mobility is impaired. In contrast, naturally occurring mutations in PLP, including its increased expression (normal PLP over-expression), have serious functional consequences. It should be noted that significant quantities of PLP and DM-20 proteins are present in the CNS, there is also a matrix RNA for PLP in the PNS, and a small amount of protein is synthesized there, but is not included in myelin.

The cationic protein of myelin (MBP) attracts the attention of researchers due to its antigenic nature - when administered to animals, it causes an autoimmune reaction, the so-called experimental allergic encephalomyelitis, which is a model of a severe neurodegenerative disease - multiple sclerosis.

The amino acid sequence of MBP in many organisms is highly conserved. MBP is located on the cytoplasmic side of myelin membranes. It has a molecular weight of 18.5 kD and is devoid of signs of a tertiary structure. This basic protein reveals microheterogeneity during electrophoresis in alkaline conditions. Most of the mammals studied contained different amounts of MBP isoforms having a significant common part of the amino acid sequence. Molecular weight of ICBMs of mice and rats is 14 kDa. A low molecular weight MBR has the same amino acid sequences at the N- and C-terminal parts of the molecule as the rest of the ICBM, but is characterized by a reduction of about 40 amino acid residues. The ratio of these basic proteins varies during development: mature rats and mice have more ICBMs with a molecular mass of 14 kDa than MBDs with a molecular weight of 18 kDa. Two other isoforms of ICBMs, also found in many organisms, have a molecular weight of 21.5 and 17 kDa, respectively. They are formed by attachment to the main structure of a polypeptide sequence of about 3 kDa.

Electrophoretic separation of myelin proteins reveals proteins with a higher molecular weight. Their number depends on the type of organism. For example, a mouse and a rat can contain such proteins up to 30% of the total. The content of these proteins also varies depending on the age of the animal: the younger it is, the less in my brain myelin, but the more proteins in it have a higher molecular weight.

The enzyme 2 '3'-cyclic nucleotide Z'-phosphodiesterase (CNP) accounts for several percent of the total myelin protein content in CNS cells. This is much more than in other types of cells. CNP protein is not the main component of compact myelin, it is concentrated only in certain areas of the myelin sheath associated with the cytoplasm of the oligodendrocyte. The protein is localized in the cytoplasm, but part of it is associated with the membrane cytoskeleton - F-actin and tubulin. The biological function of CNP can be to regulate the structure of the cytoskeleton to accelerate growth processes and differentiation in oligodendrocytes.

Myelin-associated glycoprotein (MAG), a minor component of the purified myelin in quantitative terms, has a molecular weight of 100 kDa, is present in the CNS in a small amount (less than 1% of the total protein). MAG has a single transmembrane domain that separates the highly glycosylated extracellular portion of the molecule composed of five immunoglobulin-like domains from the intracellular domain. Its total structure is similar to the neuronal cell adhesion protein (NCAM).

MAG is not present in a compact, multilamellar myelin, but is located in the peri-axonal membranes of oligodendrocytes forming myelin layers. Recall that the peri-axonal membrane of the oligodendrocyte is most closely located to the plasma membrane of the axon, but nevertheless these two membranes do not merge, but are separated by an extracellular gap. A similar feature of the localization of MAG, as well as the fact that this protein belongs to the immunoglobulin superfamily, confirms its involvement in the processes of adhesion and transmission of information (signaling) between axolemma and myelin-forming oligodendrocytes during myelination. In addition, MAG is one of the components of the white matter of the CNS, which inhibits the growth of neurites in tissue culture.

Of the other glycoproteins of white matter and myelin, a minor myelinolygodendrocytic glycoprotein (Myelin-oligodendrocytic glycoprotein, MOG) should be noted. MOG is a transmembrane protein containing a single immunoglobulin-like domain. Unlike MAG, which is located in the inner layers of myelin, MOG is localized in its surface layers, so it can participate in the transfer of extracellular information to the oligodendrocyte.

Small amounts of characteristic membrane proteins can be identified by polyacrylamide gel electrophoresis (PAGE) (eg, tubulin). High-resolution electrophoresis demonstrates the presence of other minor bands of protein; they can be associated with the presence of a number of myelin sheath enzymes.

Proteins of myelin PNS

Myelin PNS contains some unique proteins, as well as some proteins common with proteins of myelin CNS.

Р0 - the main protein myelin PNS, has a molecular mass of 30 kDa, is more than half the proteins myelin PNS. It is interesting to note that although it differs from PLP in the amino acid sequence, the paths of post-translational modification and structure, nevertheless, both these proteins are equally important for the formation of the myelin structure of the CNS and PNS.

The content of MBP in myelin of PNS is 5-18% of the total amount of protein, in contrast to the CNS, where its fraction reaches one-third of the total protein. The same four forms of MBP protein with molecular weights of 21, 18.5, 17 and 14kDa, respectively, found in myelin of the central nervous system are also present in the PNS. In adult rodents MBP with a molecular mass of 14 kDa (according to the classification of peripheral myelin proteins it was named "Pr") is the most significant component of all cationic proteins. In the myelin of the PNS, there is also MBP with a molecular mass of 18 kDa (in this case it is called "protein P1"). It should be noted that the importance of the protein family of MBP is not so great for myelin structure of PNS, as for the CNS.

Glycoproteins of myelin PNS

The compact myelin PNS contains a glycoprotein with a molecular mass of 22 kDa, called the peripheral myelin protein 22 (PMP-22), whose proportion is less than 5% of the total protein content. PMP-22 has four transmembrane domains and one glycosylated domain. This protein does not play a significant structural role. However, the anomalies of the pmr-22 gene are responsible for certain hereditary human neuropathologies.

Several decades ago it was believed that myelin creates an inert membrane that does not perform any biochemical functions. However, later in myelin, a large number of enzymes involved in the synthesis and metabolism of myelin components were detected. A number of enzymes present in myelin are included in the metabolism of phosphoinositides: phosphatidylinositolkinase, diphosphatidylinositolkinase, corresponding phosphatases and diglyceride kinases. These enzymes are of interest because of the high concentration of polyphosphoinositides in myelin and their rapid metabolism. There is evidence of the presence in myelin of muscarinic cholinergic receptors, G-proteins, phospholipases C and E, protein kinase C.

Myelin PNS revealed Na / K-ATPase, which carries the transport of monovalent cations, as well as 6'-nucleotidase. The presence of these enzymes suggests that myelin can actively participate in axonal transport.