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Published 9 June 2003. doi:10.1083/jcb.200303082
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© The Rockefeller University Press, 0021-9525/2003/6/845 $5.00
The Journal of Cell Biology, Volume 161, Number 5, 845-851

Report

 Regulation of leading edge microtubule and actin dynamics downstream of Rac1

Torsten Wittmann1, Gary M. Bokoch2 and Clare M. Waterman-Storer1

1 Department of Cell Biology and Institute for Childhood and Neglected Diseases, The Scripps Research Institute, La Jolla, CA 92037
2 Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037

Address correspondence to Clare M. Waterman-Storer, The Scripps Research Institute, Dept. of Cell Biology, CB 163, 10550 North Torrey Pines Rd., La Jolla, CA 92037. Tel.: (858) 784-9764. Fax: (858) 784-9779. E-mail: waterman{at}scripps.edu

Actin in migrating cells is regulated by Rho GTPases. However, Rho proteins might also affect microtubules (MTs). Here, we used time-lapse microscopy of PtK1 cells to examine MT regulation downstream of Rac1. In these cells, "pioneer" MTs growing into leading-edge protrusions exhibited a decreased catastrophe frequency and an increased time in growth as compared with MTs further from the leading edge. Constitutively active Rac1(Q61L) promoted pioneer behavior in most MTs, whereas dominant-negative Rac1(T17N) eliminated pioneer MTs, indicating that Rac1 is a regulator of MT dynamics in vivo. Rac1(Q61L) also enhanced MT turnover through stimulation of MT retrograde flow and breakage. Inhibition of p21-activated kinases (Paks), downstream effectors of Rac1, inhibited Rac1(Q61L)-induced MT growth and retrograde flow. In addition, Rac1(Q61L) promoted lamellipodial actin polymerization and Pak-dependent retrograde flow. Together, these results indicate coordinated regulation of the two cytoskeletal systems in the leading edge of migrating cells.

Key Words: cell motility; cytoskeleton; tubulin; Rho GTPases; p21-activated kinase

The online version of this article includes supplemental material.

* Abbreviations used in this paper: MT, microtubule; Pak, p21-activated kinase; PBD/ID(H83L), mutated p21-binding and autoinhibitory domains of Pak1.


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