N-WASP is required for membrane wrapping and myelination by Schwann cells.
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.
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Nurit
N
Novak
Vered
V
Bar
Helena
H
Sabanay
Shahar
S
Frechter
Martine
M
Jaegle
Scott B
SB
Snapper
Dies
D
Meijer
Elior
E
Peles
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000502:physiology*; D012583:Schwann Cells / Q000166:cytology* / Q000378:metabolism*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000172:deficiency / Q000378:metabolism*
C495772:Wasl protein, mouse; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal
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