Abstract
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.
Keywords
RAC1Cell biologyMicrotubuleActinCytoskeletonBiologyRac GTP-Binding ProteinsMicrotubule polymerizationChemistryTubulinSignal transductionCellBiochemistry
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Publication Info
- Year
- 2003
- Type
- article
- Volume
- 161
- Issue
- 5
- Pages
- 845-851
- Citations
- 267
- Access
- Closed
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Cite This
Torsten Wittmann,
Gary Bokoch,
Clare M. Waterman
(2003).
Regulation of leading edge microtubule and actin dynamics downstream of Rac1.
The Journal of Cell Biology
, 161
(5)
, 845-851.
https://doi.org/10.1083/jcb.200303082
Identifiers
- DOI
- 10.1083/jcb.200303082