article published Anika Steffen author Markus Ladwein author Georgi A Dimchev author 38C393BE-F248-11E8-B48F-1D18A9856A87 Anke Hein author Lisa Schwenkmezger author Stefan Arens author Kathrin Ladwein author J. Holleboom author Florian Schur author 48AD8942-F248-11E8-B48F-1D18A9856A870000-0003-4790-8078 John Small author Janett Schwarz author Ralf Gerhard author Jan Faix author Theresia Stradal author Cord Brakebusch author Klemens Rottner author 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. Company of Biologists2013 10.1242/jcs.118232 126204572 - 4588 yes 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.” <i>Journal of Cell Science</i>. Company of Biologists, 2013. <a href="https://doi.org/10.1242/jcs.118232">https://doi.org/10.1242/jcs.118232</a>. 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. <i>Journal of Cell Science</i>. Company of Biologists. <a href="https://doi.org/10.1242/jcs.118232">https://doi.org/10.1242/jcs.118232</a> A. Steffen <i>et al.</i>, “Rac function is crucial for cell migration but is not required for spreading and focal adhesion formation,” <i>Journal of Cell Science</i>, vol. 126, no. 20. Company of Biologists, pp. 4572–4588, 2013. Steffen, Anika, et al. “Rac Function Is Crucial for Cell Migration but Is Not Required for Spreading and Focal Adhesion Formation.” <i>Journal of Cell Science</i>, vol. 126, no. 20, Company of Biologists, 2013, pp. 4572–88, doi:<a href="https://doi.org/10.1242/jcs.118232">10.1242/jcs.118232</a>. 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. <i>Journal of Cell Science</i>. 2013;126(20):4572-4588. doi:<a href="https://doi.org/10.1242/jcs.118232">10.1242/jcs.118232</a> A. Steffen, M. Ladwein, G.A. Dimchev, A. Hein, L. Schwenkmezger, S. Arens, K. Ladwein, J. Holleboom, F.K. Schur, J. Small, J. Schwarz, R. Gerhard, J. Faix, T. Stradal, C. Brakebusch, K. Rottner, Journal of Cell Science 126 (2013) 4572–4588. Steffen A, Ladwein M, Dimchev GA, Hein A, Schwenkmezger L, Arens S, Ladwein K, Holleboom J, Schur FK, 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. 8112018-12-11T11:48:38Z2021-01-12T08:16:57Z