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PMID: 12796474 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Regulation of leading edge microtubule and actin dynamics downstream of Rac1.

The Journal of cell biology ·Vol. 161 ·No. 5 ·2003-06-09 ·Pages 845-51

Wittmann T, Bokoch GM, Waterman-Storer CM

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.

MeSH Terms
Actin Cytoskeleton/metabolism Animals Cell Movement/physiology Cell Polarity/physiology Cells, Cultured Enzyme Inhibitors/pharmacology Eukaryotic Cells/metabolism Microscopy, Video Microtubules/metabolism Mutation/genetics Protein Serine-Threonine Kinases/antagonists & inhibitors,metabolism Pseudopodia/metabolism p21-Activated Kinases rac1 GTP-Binding Protein/genetics,metabolism
Chemicals
Enzyme Inhibitors Protein Serine-Threonine Kinases p21-Activated Kinases rac1 GTP-Binding Protein
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Wittmann Torsten
Department of Cell Biology and Institute for Childhood and Neglected Diseases, La Jolla, CA 92037, USA.
Bokoch Gary M
Waterman-Storer Clare M
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200303082
Published
2003-06-09
Pages
845-51
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2172968
Subset
IM
Grants
NIGMS NIH HHS · R01 GM039434 · United States
NIGMS NIH HHS · R01 GM061804 · United States
NIGMS NIH HHS · GM39434 · United States
NIGMS NIH HHS · GM61804 · United States
External Links
PubMed source DOI: 10.1083/jcb.200303082 PMC Full Text View journal details
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