TY - JOUR
T1 - β1 integrin activates Rac1 in Schwann cells to generate radial lamellae during axonal sorting and myelination
AU - Nodari, Alessandro
AU - Zambroni, Desirée
AU - Quattrini, Angelo
AU - Court, Felipe A.
AU - D'Urso, Alessandra
AU - Recchia, Alessandra
AU - Tybulewicz, V. L J
AU - Wrabetz, Lawrence
AU - Feltri, M. Laura
PY - 2007/6/18
Y1 - 2007/6/18
N2 - Myelin is a multispiraled extension of glial membrane that surrounds axons. How glia extend a surface many-fold larger than their body is poorly understood. Schwann cells are peripheral glia and insert radial cytoplasmic extensions into bundles of axons to sort, ensheath, and myelinate them. Laminins and β1 integrins are required for axonal sorting, but the downstream signals are largely unknown. We show that Schwann cells devoid of β1 integrin migrate to and elongate on axons but cannot extend radial lamellae of cytoplasm, similar to cells with low Rac1 activation. Accordingly, active Rac1 is decreased in β1 integrin-null nerves, inhibiting Rac1 activity decreases radial lamellae in Schwann cells, and ablating Rac1 in Schwann cells of transgenic mice delays axonal sorting and impairs myelination. Finally, expressing active Rac1 in β1 integrin-null nerves improves sorting. Thus, in creased activation of Rac1 by β1 integrins allows Schwann cells to switch from migration/elongation to the extension of radial membranes required for axonal sorting and myelination.
AB - Myelin is a multispiraled extension of glial membrane that surrounds axons. How glia extend a surface many-fold larger than their body is poorly understood. Schwann cells are peripheral glia and insert radial cytoplasmic extensions into bundles of axons to sort, ensheath, and myelinate them. Laminins and β1 integrins are required for axonal sorting, but the downstream signals are largely unknown. We show that Schwann cells devoid of β1 integrin migrate to and elongate on axons but cannot extend radial lamellae of cytoplasm, similar to cells with low Rac1 activation. Accordingly, active Rac1 is decreased in β1 integrin-null nerves, inhibiting Rac1 activity decreases radial lamellae in Schwann cells, and ablating Rac1 in Schwann cells of transgenic mice delays axonal sorting and impairs myelination. Finally, expressing active Rac1 in β1 integrin-null nerves improves sorting. Thus, in creased activation of Rac1 by β1 integrins allows Schwann cells to switch from migration/elongation to the extension of radial membranes required for axonal sorting and myelination.
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U2 - 10.1083/jcb.200610014
DO - 10.1083/jcb.200610014
M3 - Article
C2 - 17576799
AN - SCOPUS:34250740938
VL - 177
SP - 1063
EP - 1075
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 6
ER -