Cellular contacts in myelinated fibers of the peripheral nervous system

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Abstract from Med Sci (Paris). 2005 Feb;21(2):162-9

Cellular contacts in myelinated fibers of the peripheral nervous system

Oguievetskaia K, Cifuentes- C, Girault JA, Goutebroze L.

Laboratoire de transduction du signal et plasticite dans le systeme nerveux,

Inserm U.536 et Universite Pierre et Marie Curie, Institut du Fer a Moulin, 17,

rue du Fer a Moulin, 75005 Paris, France.

Myelination allows the fast propagation of action potentials at a low energetic

cost. It provides an insulating myelin sheath regularly interrupted at nodes of

Ranvier where voltage-gated Na+ channels are concentrated. In the peripheral

nervous system, the normal function of myelinated fibers requires the formation

of highly differentiated and organized contacts between the myelinating Schwann

cells, the axons and the extracellular matrix. Some of the major molecular

complexes that underlie these contacts have been identified. Compact myelin

which forms the bulk of the myelin sheath results from the fusion of the Schwann

cell membranes through the proteins P0, PMP22 and MBP. The basal lamina of

myelinating Schwann cells contains laminin-2 which associates with the glial

complex dystroglycan/DPR2/L-periaxin. Non compact myelin, found in paranodal

loops, periaxonal and abaxonal regions, and Schmidt-Lanterman incisures,

presents reflexive adherens junctions, tight junctions and gap junctions, which

contain cadherins, claudins and connexins, repectively. Axo-glial contacts

determine the formation of distinct domains on the axon, the node, the paranode,

and the juxtaparanode. At the paranodes, the glial membrane is tightly attached

to the axolemma by septate-like junctions. Paranodal and juxtaparanodal axoglial

complexes comprise an axonal transmembrane protein of the NCP family associated

in cis and in trans with cell adhesion molecules of the immunoglobulin

superfamily (IgSF-CAM). At nodes, axonal complexes are composed of Na+ channels

and IgSF-CAMs. Schwann cell microvilli, which loosely cover the node, contain

ERM proteins and the proteoglycans syndecan-3 and -4. The fundamental role of

the cellular contacts in the normal function of myelinated fibers has been

supported by rodent models and the detection of genetic alterations in patients

with peripheral demyelinating neuropathies such as Charcot-Marie-Tooth diseases.

Understanding more precisely their molecular basis now appears essential as a

requisite step to further examine their involvement in the pathogenesis of

peripheral neuropathies in general.

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