During peripheral nerve myelination, Schwann cells sort larger axons, ensheath them, and eventually wrap their membrane to form the myelin sheath. These processes involve extensive changes in cell shape, but the exact mechanisms involved are still unknown. Neural Wiskott-Aldrich syndrome protein (N-WASP) integrates various extracellular signals to control actin dynamics and cytoskeletal reorganization through activation of the Arp2/3 complex. By generating mice lacking N-WASP in myelinating Schwann cells, we show that N-WASP is crucial for myelination. In N-WASP-deficient nerves, Schwann cells sort and ensheath axons, but most of them fail to myelinate and arrest at the promyelinating stage. Yet, a limited number of Schwann cells form unusually short internodes, containing thin myelin sheaths, with the occasional appearance of myelin misfoldings. These data suggest that regulation of actin filament nucleation in Schwann cells by N-WASP is crucial for membrane wrapping, longitudinal extension, and myelination.

dx.doi.org/10.1083/jcb.201010013, hdl.handle.net/1765/31708
The Journal of Cell Biology
Erasmus MC: University Medical Center Rotterdam

N-WASP is required for membrane wrapping and myelination by Schwann cells. (2011). N-WASP is required for membrane wrapping and myelination by Schwann cells. The Journal of Cell Biology, 192(2), 243–250. doi:10.1083/jcb.201010013