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.
Specific disruption of a Schwann cell dystrophin-related protein complex in a demyelinating neuropathy / Diane L., Sherman; Fabrizi, Cinzia; C., Stewart Gillespie; Peter J., Brophy. - In: NEURON. - ISSN 0896-6273. - 30:3(2001), pp. 677-687. [10.1016/s0896-6273(01)00327-0]
Specific disruption of a Schwann cell dystrophin-related protein complex in a demyelinating neuropathy
FABRIZI, CINZIA;
2001
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.