Rac function is crucial for cell migration but is not required for spreading and focal adhesion formation

A. Steffen, M. Ladwein, G.A. Dimchev, A. Hein, L. Schwenkmezger, S. Arens, K. Ladwein, J. Holleboom, F. Schur, J. Small, J. Schwarz, R. Gerhard, J. Faix, T. Stradal, C. Brakebusch, K. Rottner, Journal of Cell Science 126 (2013) 4572–4588.

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Abstract
Cell migration is commonly accompanied by protrusion of membrane ruffles and lamellipodia. In two-dimensional migration, protrusion of these thin sheets of cytoplasm is considered relevant to both exploration of new space and initiation of nascent adhesion to the substratum. Lamellipodium formation can be potently stimulated by Rho GTPases of the Rac subfamily, but alsoby RhoG or Cdc42. Here we describe viable fibroblast cell lines geneticallydeficient for Rac1 that lack detectable levels of Rac2 and Rac3. Rac-deficient cells were devoid of apparent lamellipodia, but these structures were restored by expression of either Rac subfamily member, but not by Cdc42 or RhoG. Cells deficient in Rac showed strong reduction in wound closure and random cell migration and a notable loss of sensitivity to a chemotactic gradient. Despite these defects, Rac-deficient cells were able to spread, formed filopodia and established focal adhesions. Spreading in these cells was achieved by the extension of filopodia followed by the advancement of cytoplasmic veils between them. The number and size of focal adhesions as well as their intensity were largely unaffected by genetic removal of Rac1. However, Rac deficiency increased the mobility of different components in focal adhesions, potentially explaining how Rac - although not essential - can contribute to focal adhesion assembly. Together, our data demonstrate that Rac signaling is essential for lamellipodium protrusion and for efficient cell migration, but not for spreading or filopodium formation. Our findings also suggest that Rac GTPases are crucial to the establishment or maintenance of polarity in chemotactic migration.
Publishing Year
Date Published
2013-01-01
Journal Title
Journal of Cell Science
Acknowledgement
This work was supported in part by the Deutsche Forschungsgemeinschaft [grants within programs SFB621 to K.R., and FOR629 and SFB629 to T.E.B.S.]. Deposited in PMC for immediate release. We thank Brigitte Denker and Gerd Landsberg for excellent technical assistance. We are grateful to Robert Geffers (HZI Braunschweig, Germany) for microarray analyses and to Mirko Himmel (UKE Hamburg, Germany) for valuable advice on FRAP analysis.
Volume
126
Issue
20
Page
4572 - 4588
IST-REx-ID

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Steffen A, Ladwein M, Dimchev GA, et al. Rac function is crucial for cell migration but is not required for spreading and focal adhesion formation. Journal of Cell Science. 2013;126(20):4572-4588. doi:10.1242/jcs.118232
Steffen, A., Ladwein, M., Dimchev, G. A., Hein, A., Schwenkmezger, L., Arens, S., … Rottner, K. (2013). Rac function is crucial for cell migration but is not required for spreading and focal adhesion formation. Journal of Cell Science, 126(20), 4572–4588. https://doi.org/10.1242/jcs.118232
Steffen, Anika, Markus Ladwein, Georgi A Dimchev, Anke Hein, Lisa Schwenkmezger, Stefan Arens, Kathrin Ladwein, et al. “Rac Function Is Crucial for Cell Migration but Is Not Required for Spreading and Focal Adhesion Formation.” Journal of Cell Science 126, no. 20 (2013): 4572–88. https://doi.org/10.1242/jcs.118232.
A. Steffen et al., “Rac function is crucial for cell migration but is not required for spreading and focal adhesion formation,” Journal of Cell Science, vol. 126, no. 20, pp. 4572–4588, 2013.
Steffen A, Ladwein M, Dimchev GA, Hein A, Schwenkmezger L, Arens S, Ladwein K, Holleboom J, Schur F, Small J, Schwarz J, Gerhard R, Faix J, Stradal T, Brakebusch C, Rottner K. 2013. Rac function is crucial for cell migration but is not required for spreading and focal adhesion formation. Journal of Cell Science. 126(20), 4572–4588.
Steffen, Anika, et al. “Rac Function Is Crucial for Cell Migration but Is Not Required for Spreading and Focal Adhesion Formation.” Journal of Cell Science, vol. 126, no. 20, Company of Biologists, 2013, pp. 4572–88, doi:10.1242/jcs.118232.

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