Myelin protein

Antibodies typically are able to recognize peptide sequences as small as 5-6 amino acids in length. For instance, IgE auto-antibodies were found to have clinical significance in multiple sclerosis by binding specifically to short 5- and 6-amino acid epitopes on the surface of myelin proteins (Mikol et al., 2006). 

Mikol, D.D., Ditlow, C., Usatin, D., Biswas, P., Kalbfleisch, J., Milner, A., and Calenoff, E. (2006) Serum IgE reactive against small myelin protein-derived peptides is increased in multiple sclerosis patients. 

Central nervous system myelin contains some unique proteins 58 Peripheral nervous system myelin also contains unique proteins 63 Some classically defined myelin proteins are common to both peripheral and central myelin 64... 

Trembler mouse (PMP-22) AD Peripheral myelin protein-22 (PMP-22) Hypomyelination specific for the PNS caused by point mutations in transmembrane domains see text 1,45... 

Taiep rat (acronym trembling, ataxia, immobility, epilepsy, paralysis) AR Unknown Impaired myelin formation followed by demyelination in the CNS accumulation of microtubules in oligodendrocytes interferes with transport of myelin proteins or mRNAs see text 49... 

P2 protein. PNS myelin contains a positively charged protein different from MBP that is referred to as P2 (Mr — 15,000). It is unrelated in sequence to MBP and is a member of a family of cytoplasmic fatty acid binding proteins (FABP) that are present in a variety of cell types [25]. The amount of P2 protein is variable among species, accounting for about 15% of total protein in bovine PNS myelin, 5% in humans and less than 1% in rodents. P2 protein is generally considered a PNS myelin protein but it is expressed in small amounts in CNS myelin sheaths of some species. P2 is an antigen for experimental allergic neuritis, the PNS counterpart of EAE (see Chs 36 and 38). P2 appears to be present in the major dense line of myelin sheaths, where it may play a structural role similar to MBP... 

Some classically defined myelin proteins are common to both peripheral and central myelin. 

Myelin basic protein. In PNS myelin, MBP varies from approximately 5% to 18% of total protein, in contrast to the CNS, where it is close to 30% [ 1 ]. In rodents, the same four 21,18.5,17 and 14kDa MBPs found in the CNS are present in the PNS. In adult rodents, the 14kDa MBP is the most prominent component and is termed Pr in the PNS nomenclature. The 18.5 kDa component is present and is often referred to as the P, protein in the nomenclature of peripheral myelin proteins. Another species-specific variation in human PNS is that the major basic protein is not the 18.5 kDa isoform that is most prominent in the CNS but rather a form of about 17 kDa. It appears that MBP does not play as critical a role in myelin structure in the PNS as it does in the CNS. For example, the shiverer mutant mouse, which expresses no MBP (Table 4-2), has a greatly reduced amount of CNS myelin, with no compaction of the major dense line. By contrast, shiverer PNS has essentially normal myelin,both in amount and structure, despite the absence of MBP. This CNS/PNS difference in the role of MBP is probably because the cytoplasmic domain of P0 has an important role in stabilizing the major dense line of PNS myelin. Animals doubly deficient for P0 and MBP have a more severe defect in compaction of the PNS major dense line than P0-null mice, which indicates that both proteins contribute to compaction of the cytoplasmic surfaces in PNS myelin [23],... 

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... 

Two allelic trembler mutations, which affect only the PNS, result from different point mutations in transmembrane domains of peripheral myelin protein-22 (PMP-22) [1,45] (Table 4-2). The trembler phenotypes are characterized by hypomyelination, continued Schwann cell proliferation and partial paralysis of the limbs. These murine mutants are animal models for some of the inherited human neuropathies caused by abnormalities of the... 

The more recently identified taiep rat mutant (Table 4-2) has impaired accumulation of CNS myelin for up to 2 months followed by a period of demyelination [49], Adult taiep rats have only 10-25% of the normal amount of CNS myelin. The primary genetic lesion has not yet been identified but the mutant oligodendrocytes exhibit an abnormal accumulation of microtubules during development, suggesting that the mutation may involve a microtubule-associated protein. Biochemical and immu-nocytochemical studies indicate that excessive microtubule accumulation interferes with transport of myelin proteins and/or their mRNAs, eventually leading to a failure of myelin maintenance [49]. 

Eichberg, J. and Iyer, S. Minireview Phosphorylation of myelin proteins Recent Advances. Neurochem. Res. 21, 527-535,1996. 

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. 

Members of this family of molecules may have only one Ig-like domain, as is the case for the myelin protein P0, or, as for most of the family, have many Ig domains. In addition to the subclassification of Ig domains into V-, C- and C2-like domains, Ig family members can be broadly divided into three general classes [8] (a) those that have only Ig-like domains (b) those that have Ig domains and additional domains that resemble regions of the ECM component fibronectin, termed FN-like domains and (c) those that have Ig domains and motifs other than FN-like domains. Moreover, any one Ig family member may have many isoforms, which may differ in the length of the cytoplasmic domain, in their post-translational modifications and whether they are membrane-spanning or glycosylphos-phatidylinositol (GPI)-anchored proteins (see Box 3-1). Also, additional amino acid sequences inserted in the extracellular domain may distinguish isoforms of a particular IgCAM. While it is not known how the majority... 

Lemke, G., Lamar, E. and Patterson, J. Isolation and analysis of the gene encoding peripheral myelin-protein zero. Neuron 1 73-83,1988. 

Neuropathies can result from mutations that alter the structure or level of expression of PNS myelin proteins (e.g. overexpression of PMP22 in Charcot-Marie-Tooth syndrome (CMT) type 1A), the metabolism of myelin lipids (e.g. metachromatic leukodystrophy), or the capacity of PNS neurons to support their axons in patients with CMT caused by mutations of KIF1B [4] or NF-L [5, 6]. Both acquired and inherited amyloid neuropathies can result from the deposition of poorly soluble proteins, for example cryoglobulins or mutant transthyretins, in and around endoneurial bloodvessels [7-9]. 

Gabriel, C. M., Hughes, R. A., Moore, S. E., Smith, J. J. and Walsh, F. S. Induction of experimental autoimmune neuritis with peripheral myelin protein-22. Brain 121 1895-1902,1998. 

Laouini, D., Kennou, M. R, Khoufi, S. and Dellagi, K. Antibodies to human myelin proteins and gangliosides in patients with acute neuroparalytic accidents induced by brain-derived rabies vaccine. /. Neuroimmunol. 91 63-72, 1998. 

Suter, U., Moskow, J. J., Welcher, A. A. et al. A leucine-to-proline mutation in the putative first transmembrane domain of the 22-kDa peripheral myelin protein in the trembler-J mouse. Proc. Natl Acad. Sci. U.S.A. 89 4382-4386,1992. 

What is not clear is the specificity of the T cells. There are numerous studies of T cell reactivity to myelin antigens such as MBP, PLP and MOG, all of which are enceph-alitogenic in animals. However, the evidence taken as a whole has failed to demonstrate a substantially increased response to these antigens in most patients with MS compared to healthy controls. Nevertheless, at this time, MOG appears to be a leading candidate among myelin proteins to be an important target in the autoimmune aspects in many patients because of (1) its accessibility to immune attack due to its surface localization on oligodendrocytes ... 

NRTN neurturin PMP (i) peripheral myelin protein (ii) peroxisomal... 

Inouye, H., and Kirschner, D. A. (1991). Folding and function of the myelin proteins from primary sequence data. / Neurosci. Res. 28, 1-17. 

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