Myelin and

The liquid crystalline state may be identified as a distinct and unique state of matter which is characterised by properties which resemble those of both solids and liquids. It was first recognised in the middle of the last century through the study of nerve myelin and derivatives of cholesterol. The research in the area really gathered momentum, however, when as a result of the pioneering work of Gray in the early 1970 s organic compounds exhibiting liquid crystalline properties were shown to be suitable to form the basis of display devices in the electronic products. 

The afferent fibres differ in their conduction velocity and degree of myelination, and can be distinguished by their diameter. The large diameter A S-fibres are myelinated by Schwann cells and hence have a fast conduction velocity. This group of nerve fibres innervates receptors in the dermis and is involved in the transmission of low-threshold, non-noxious information, such as touch. The A5-fibre is less densely myelinated and conveys both non-noxious and noxious sensory information. The unmyelinated C-fibre conveys high-threshold noxious inputs and has the slowest conduction velocity of all three fibre types. 

X106 years) Development of myelin and of mid-brain. Enlarged cortex... 

FIGURE 1-15 A myelinating oligodendrocyte, nucleus (N), from the spinal cord of a 2-day-old kitten extends cytoplasmic connections to at least two myelin sheaths arrows). Other myelinated and unmyelinated fibers at various stages of development, as well as glial processes, are seen in the surrounding neuropil. Xl2,750. 

TABLE 4-1 Composition of central nervous system myelin and brain... 

It is noteworthy that the axonal degeneration that occurs in the PNS of MAG-null mice is not observed in the CNS, possibly because other CNS myelin proteins enhance axonal stability. These could include PLP and/or CNP, both of which are needed for axonal stability in the CNS where they are present in much higher concentration. In summary, it appears that the most important function of MAG in the PNS is transmitting a signal from Schwann cells to axons that is needed for the stability of myelinated axons, whereas its principal function in the CNS is to transmit a signal in the reverse direction that promotes efficient myelination and oligodendrocyte vitality. 

Myelin sheaths contain other proteins, some of which have only recently been established as myelin-related. The proteins described above represent most of the well-established myelin proteins that are myelin-specific or have been studied primarily in the context of myelin and demyelinating diseases. However, myelin sheaths contain numerous other proteins in smaller amounts that are also in many other cells and/or have only been identified relatively recently. Some of these are in compact myelin but others are enriched in specialized... 

CD9 is a well-characterized hematopoietic tetraspan protein that has been shown to be present in CNS and PNS myelin, although it is present at higher levels in PNS myelin. In other cells, it is involved in integrin signaling and cell adhesion and motility. It is expressed at late stages of myelination and in the CNS is primarily found in paranodal junctions [34]. While compact CNS myelin is apparently normal in CD9-null animals, the paranodal loops are often disconnected from axonal membranes, and the transverse bands of the paranodal loops are lost. In the PNS, in addition to altered paranodes, hypermy-elination occurs. Thus, this tetraspan protein appears to act primarily at paranodes, where it is crucial for normal paranodal junctions. 

A few enzymes, such as the previously mentioned CNP, are believed to be fairly specific for myelin/oligodendro-cytes. There is much more in the CNS than in peripheral nerve, suggesting some function more specialized to the CNS. In addition, a unique pH 7.2 cholesterol ester hydrolase is also enriched in myelin. On the other hand, there are many enzymes that are not myelin-specific but appear to be intrinsic to myelin and not contaminants. These include cAMP-stimulated kinase, calcium/calmodulin-dependent kinase, protein kinase C, a neutral protease activity and phosphoprotein phosphatases. The protein kinase C and phosphatase activities are presumed to be responsible for the rapid turnover of MBP phosphate groups, and the PLP acylation enzyme activity is also intrinsic to myelin. 

Other enzymes present in myelin include those involved in phosphoinositide metabolism phosphatidylinositol kinase, diphosphoinositide kinase, the corresponding phosphatases and diglyceride kinases. These are of interest because of the high concentration of polyphosphoinositides of myelin and the rapid turnover of their phosphate groups. This area of research has expanded towards characterization of signal transduction system(s), with evidence of G proteins and phospholipases C and D in myelin. 

Small amounts of proteins characteristic of cells and membranes in general can also be found in myelin. There is evidence that tubulin is an authentic myelin-related component (Fig. 4-12B, D, CNS myelin). The 48kDa myelin/oligodendrocyte-specific protein (MOSP) is a component found only in CNS myelin and oligodendroglial membranes, which appears to associate with tubulin [41]. 

Frank, M. MAL, a proteolipid in glycosphingolipid enriched domains functional implications in myelin and beyond. Prog. Neurobiol. 60, 531-544, 2000. 

Erne, B., Sansano, S., Frank, M. et al. Rafts in adult peripheral nerve myelin contain major structural myelin proteins and myelin and lymphocyte protein (MAL) and CD59 as specific markers. /. Neurochem. 82, 550-562, 2002. 

Cell adhesion molecules (CAMs) play critical roles in all facets of nervous system development and maintenance. Important phenomena in which CAMs are involved include initial formation of the neural tube and the neural crest, migration of all neurons and glial cells, axonal outgrowth and guidance, target selection, synaptic stabilization and plasticity, myelination and nerve regeneration after injury (see Chs 4,24,28-30 and 53). Adhesion molecules interact with each other and with nonadhesive cell-surface and/or cytoplasmic molecules, and, in the two... 

Filbin, M. T. Myelin-associated glycoprotein a role in myelination and in the inhibition of axonal regeneration Curr. Opin. Neurobiol. 5 588-595,1995. 

Giese, K. P.,Martini, R., Lemke, G., Soriano, P. and Schachner, M. Mouse P0 gene disruption leads to hypomyelination, abnormal expression of recognition molecules, and degeneration of myelin and axons. Cell 71 565-576,1992. 

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