Specific disruption of a schwann cell dystrophin-related protein complex in a demyelinating neuropathy.
Dystroglycan-dystrophin complexes are believed to have structural and signaling functions by linking extracellular matrix proteins to the cytoskeleton and cortical signaling molecules. Here we characterize a dystroglycan-dystrophin-related protein 2 (DRP2) complex at the surface of myelin-forming Schwann cells. The complex is clustered by the interaction of DRP2 with L-periaxin, a homodimeric PDZ domain-containing protein. In the absence of L-periaxin, DRP2 is mislocalized and depleted, although other dystrophin family proteins are unaffected. Disruption of the DRP2-dystroglycan complex is followed by hypermyelination and destabilization of the Schwann cell-axon unit in Prx(-/-) mice. Hence, the DRP2-dystroglycan complex likely has a distinct function in the terminal stages of PNS myelinogenesis, possibly in the regulation of myelin thickness.
Sherman
D L
DL
Department of Preclinical Veterinary Sciences, University of Edinburgh, EH9 1QH, Edinburgh, United Kingdom.
Fabrizi
C
C
Gillespie
C S
CS
Brophy
P J
PJ
D000818:Animals; D001369:Axons / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002607:Charcot-Marie-Tooth Disease / Q000378:metabolism* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000378:metabolism*; D049030:Dystroglycans; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins; D009186:Myelin Sheath / Q000737:chemistry / Q000378:metabolism; D012583:Schwann Cells / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*
D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009124:Muscle Proteins; C099589:dystrophin-related protein 2; C086745:periaxin; D049030:Dystroglycans