Specific disruption of a Schwann cell dystrophin-related protein complex in a demyelinating neuropathy

Dystroglycan-dystrophin complexes are believed to have structural and signa ling functions by linking extracellular matrix proteins to the cytoskeleton and cortical signaling molecules. Here we characterize a dystroglycan-dyst rophin-related protein 2 (DRP2) complex at the surface of myelin-forming Sc hwann cells. The complex is clustered by the interaction of DRP2 with L-per iaxin, a homodimeric PDZ domain-containing protein. In the absence of L-per iaxin, DRP2 is mislocalized and depleted, although other dystrophin family proteins are unaffected. Disruption of the DRP2-dystroglycan complex is fol lowed by hypermyelination and destabilization of the Schwann cell-axon unit in Prx(-/-) mice. Hence, the DRP2-dystroglycan complex likely has a distin ct function in the terminal stages of PNS myelinogenesis, possibly in the r egulation of myelin thickness.