Beta1 integrin activates Rac1 in Schwann cells to generate radial lamellae during axonal sorting and myelination.
Author(s)
Type
Journal Article
Abstract
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 beta1 integrins are required for axonal sorting, but the downstream signals are largely unknown. We show that Schwann cells devoid of beta1 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 beta1 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 beta1 integrin-null nerves improves sorting. Thus, increased activation of Rac1 by beta1 integrins allows Schwann cells to switch from migration/elongation to the extension of radial membranes required for axonal sorting and myelination.
Date Issued
2007-06-18
Date Acceptance
2007-05-16
Citation
Journal of Cell Biology, 2007, 177 (6), pp.1063-1075
ISSN
0021-9525
Publisher
Rockefeller University Press
Start Page
1063
End Page
1075
Journal / Book Title
Journal of Cell Biology
Volume
177
Issue
6
Copyright Statement
© 2007 Rockefeller University Press
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/17576799
PII: jcb.200610014
Subjects
Animals
Axons
Cell Movement
Cell Surface Extensions
Integrin beta1
Laminin
Mice
Mice, Transgenic
Myelin Sheath
Neuropeptides
Rats
Schwann Cells
rac GTP-Binding Proteins
rac1 GTP-Binding Protein
Publication Status
Published
Coverage Spatial
United States