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β1 integrin activates Rac1 in Schwann cells to generate radial lamellae during axonal sorting and myelination

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. Laminin...

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Autores principales: Nodari, Alessandro, Zambroni, Desirée, Quattrini, Angelo, Court, Felipe A., D'Urso, Alessandra, Recchia, Alessandra, Tybulewicz, Victor L.J., Wrabetz, Lawrence, Feltri, M. Laura
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064366/
https://www.ncbi.nlm.nih.gov/pubmed/17576799
http://dx.doi.org/10.1083/jcb.200610014
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author Nodari, Alessandro
Zambroni, Desirée
Quattrini, Angelo
Court, Felipe A.
D'Urso, Alessandra
Recchia, Alessandra
Tybulewicz, Victor L.J.
Wrabetz, Lawrence
Feltri, M. Laura
author_facet Nodari, Alessandro
Zambroni, Desirée
Quattrini, Angelo
Court, Felipe A.
D'Urso, Alessandra
Recchia, Alessandra
Tybulewicz, Victor L.J.
Wrabetz, Lawrence
Feltri, M. Laura
author_sort Nodari, Alessandro
collection PubMed
description 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, increased 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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spelling pubmed-20643662007-12-18 β1 integrin activates Rac1 in Schwann cells to generate radial lamellae during axonal sorting and myelination Nodari, Alessandro Zambroni, Desirée Quattrini, Angelo Court, Felipe A. D'Urso, Alessandra Recchia, Alessandra Tybulewicz, Victor L.J. Wrabetz, Lawrence Feltri, M. Laura J Cell Biol Research Articles 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, increased 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. The Rockefeller University Press 2007-06-18 /pmc/articles/PMC2064366/ /pubmed/17576799 http://dx.doi.org/10.1083/jcb.200610014 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Nodari, Alessandro
Zambroni, Desirée
Quattrini, Angelo
Court, Felipe A.
D'Urso, Alessandra
Recchia, Alessandra
Tybulewicz, Victor L.J.
Wrabetz, Lawrence
Feltri, M. Laura
β1 integrin activates Rac1 in Schwann cells to generate radial lamellae during axonal sorting and myelination
title β1 integrin activates Rac1 in Schwann cells to generate radial lamellae during axonal sorting and myelination
title_full β1 integrin activates Rac1 in Schwann cells to generate radial lamellae during axonal sorting and myelination
title_fullStr β1 integrin activates Rac1 in Schwann cells to generate radial lamellae during axonal sorting and myelination
title_full_unstemmed β1 integrin activates Rac1 in Schwann cells to generate radial lamellae during axonal sorting and myelination
title_short β1 integrin activates Rac1 in Schwann cells to generate radial lamellae during axonal sorting and myelination
title_sort β1 integrin activates rac1 in schwann cells to generate radial lamellae during axonal sorting and myelination
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064366/
https://www.ncbi.nlm.nih.gov/pubmed/17576799
http://dx.doi.org/10.1083/jcb.200610014
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