Rac1 GTPase controls myelination and demyelination

Abstract

After peripheral nerve injuries, Wallerian degeneration starts with a stereotypic fragmentation of myelin sheath into myelin ovoids, which occur near Schmidt-Lantermann incisures (SLI). This demyelination process requires a dramatic change in cytoskeletal structures in Schwann cells. We have recently shown that actin polymerization around SLI is an important step for cleavage of the myelin sheath. We described that Rac1 GTP ase regulates actin polymerization in SLI after injury. It has been previously reported that Rac-dependent cytoskeletal reorganization also plays an important role in myelination during the development of peripheral nerves. Thus, our findings suggest that Rac-dependent actin polymerization controls both myelination and demyelination in the peripheral nerves. We further discuss our new findings in relation to Schwann cell dedifferentiation and segmental demyelination.

Figure 1

(A) Myelination of axon by Schwann cells requires Rac GTPase-regulated actin polymerization. Actin polymerization in Schwann cells regulates extensive protrusion of cell membrane during myelination. (B) After peripheral nerve injury, active Rac GTPase localizes into wide Schmidt-Lantermann incisures (SLI) and regulates actin polymerization in SLI. Rac-dependent actin polymerization in SLI is essential for cleavage of myelin sheath into ovoids in demyelinating Schwann cells. (C) Segmental demyelination that observed in peripheral neuropathies shows axonal sparing and few myelin ovoids. The implication of Rac-dependent actin polymerization in segmental demyelination is unknown.