Stabilizing the Myelin Sheath

Science's STKE  26 Jun 2001:
Vol. 2001, Issue 88, pp. tw1
DOI: 10.1126/stke.2001.88.tw1

Schwann cells of the peripheral nervous system express periaxin, a cytosolic protein that contains a PDZ domain, a hallmark of adaptor proteins that assemble macromolecular signaling complexes. Mutations in the human periaxin gene cause the demyelinating neuropathy of Charcot-Marie-Tooth disease, and mice that lack functional periaxin develop a similar condition. Sherman et al. have now determined why periaxin is so critical. Periaxin associates with a cytoplasmic protein called DRP2, a member of the dystrophin family, whose members bind to dystroglycans, the cell-surface receptors for extracellular matrix molecules. Periaxin forms PDZ domain-mediated dimers, and hence clusters the associated dystrophin-glycoprotein complexes at the surface of Schwann cells. Disruption of this clustering destroys dystroglycan organization, thus affecting neuron-Schwann cell interaction and myelin sheath integrity.

D. L. Sherman, C. Fabrizi, C. S. Gillespie, P. J. Brophy, Specific disruption of a Schwann cell dystrophin-related protein complex in a demyelinating neuropathy. Neuron 30, 677-687 (2001). [Online Journal]