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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18 June 2007
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June 18 2007
β1 integrin activates Rac1 in Schwann cells to generate radial lamellae during axonal sorting and myelination
Alessandro Nodari,
Alessandro Nodari
1Department of Biological and Technological Research
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Desirée Zambroni,
Desirée Zambroni
1Department of Biological and Technological Research
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Angelo Quattrini,
Angelo Quattrini
2Department of Neurology, San Raffaele Scientific Institute, 20132 Milan, Italy
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Felipe A. Court,
Felipe A. Court
1Department of Biological and Technological Research
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Alessandra D'Urso,
Alessandra D'Urso
1Department of Biological and Technological Research
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Alessandra Recchia,
Alessandra Recchia
3Department of Biomedical Sciences, University of Modena and Reggio Emilia, 42100 Reggio Emilia, Italy
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Victor L.J. Tybulewicz,
Victor L.J. Tybulewicz
4National Institute for Medical Research, London NW7 1AA, England, UK
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Lawrence Wrabetz,
Lawrence Wrabetz
1Department of Biological and Technological Research
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M. Laura Feltri
M. Laura Feltri
1Department of Biological and Technological Research
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Alessandro Nodari
1Department of Biological and Technological Research
Desirée Zambroni
1Department of Biological and Technological Research
Angelo Quattrini
2Department of Neurology, San Raffaele Scientific Institute, 20132 Milan, Italy
Felipe A. Court
1Department of Biological and Technological Research
Alessandra D'Urso
1Department of Biological and Technological Research
Alessandra Recchia
3Department of Biomedical Sciences, University of Modena and Reggio Emilia, 42100 Reggio Emilia, Italy
Victor L.J. Tybulewicz
4National Institute for Medical Research, London NW7 1AA, England, UK
Lawrence Wrabetz
1Department of Biological and Technological Research
M. Laura Feltri
1Department of Biological and Technological Research
Correspondence to M. Laura Feltri: [email protected]
Abbreviations used in this paper: CA, constitutively active; DRG, dorsal root ganglia; E, embryonic day; MBP, myelin basic protein; P, postnatal day; PAK, p21-activated kinase; PBD, PAK binding domain; PLL, poly-l-lysine; SC, Schwann cell; wt, wild-type.
Received:
October 03 2006
Accepted:
May 16 2007
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2007
J Cell Biol (2007) 177 (6): 1063–1075.
Article history
Received:
October 03 2006
Accepted:
May 16 2007
Citation
Alessandro Nodari, Desirée Zambroni, Angelo Quattrini, Felipe A. Court, Alessandra D'Urso, Alessandra Recchia, Victor L.J. Tybulewicz, Lawrence Wrabetz, M. Laura Feltri; β1 integrin activates Rac1 in Schwann cells to generate radial lamellae during axonal sorting and myelination . J Cell Biol 18 June 2007; 177 (6): 1063–1075. doi: https://doi.org/10.1083/jcb.200610014
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