beta 1 integrin activates Rac1 in Schwann cells to generate radial lamellae during axonal sorting and myelination

Nodari, Alessandro; Zambroni, Desiree; Quattrini, Angelo; Court, Felipe A.; D'Urso, Alessandra; Recchia, Alessandra; Tybulewicz, Victor L. J.; Wrabetz, Lawrence; Feltri, M. Laura


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 beta 1 integrins are required for axonal sorting, but the downstream signals are largely unknown. We show that Schwann cells devoid of beta 1 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 beta 1 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 beta 1 integrin - null nerves improves sorting. Thus, in creased activation of Rac1 by beta 1 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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Título según WOS: ID WOS:000247347400013 Not found in local WOS DB
Título de la Revista: JOURNAL OF CELL BIOLOGY
Volumen: 177
Número: 6
Fecha de publicación: 2007
Página de inicio: 1063
Página final: 1075


Notas: ISI