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PMID: 17981134 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Cofilin activity downstream of Pak1 regulates cell protrusion efficiency by organizing lamellipodium and lamella actin networks.

Developmental cell ·Vol. 13 ·No. 5 ·2007-11-00 ·Pages 646-662

Delorme V, Machacek M, DerMardirossian C, Anderson KL, Wittmann T, Hanein D, Waterman-Storer C, Danuser G, Bokoch GM

Abstract

Protrusion of the leading edge of migrating epithelial cells requires precise regulation of two actin filament (F-actin) networks, the lamellipodium and the lamella. Cofilin is a downstream target of Rho GTPase signaling that promotes F-actin cycling through its F-actin-nucleating, -severing, and -depolymerizing activity. However, its function in modulating lamellipodium and lamella dynamics, and the implications of these dynamics for protrusion efficiency, has been unclear. Using quantitative fluorescent speckle microscopy, immunofluorescence, and electron microscopy, we establish that the Rac1/Pak1/LIMK1 signaling pathway controls cofilin activity within the lamellipodium. Enhancement of cofilin activity accelerates F-actin turnover and retrograde flow, resulting in widening of the lamellipodium. This is accompanied by increased spatial overlap of the lamellipodium and lamella networks and reduced cell-edge protrusion efficiency. We propose that cofilin functions as a regulator of cell protrusion by modulating the spatial interaction of the lamellipodium and lamella in response to upstream signals.

MeSH Terms
Actin Depolymerizing Factors/physiology Actins/physiology Cell Line Cell Movement Epithelial Cells/physiology Fluorescent Antibody Technique Humans Lim Kinases/metabolism Microfilament Proteins/physiology Pseudopodia/physiology Signal Transduction p21-Activated Kinases/physiology rac1 GTP-Binding Protein/metabolism
Chemicals
Actin Depolymerizing Factors Actins Microfilament Proteins LIMK1 protein, human Lim Kinases PAK1 protein, human p21-Activated Kinases rac1 GTP-Binding Protein
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Delorme Violaine
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Machacek Matthias
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
DerMardirossian Céline
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Anderson Karen L
Infectious Diseases Program, The Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
Wittmann Torsten
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Hanein Dorit
Infectious Diseases Program, The Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
Waterman-Storer Clare
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Danuser Gaudenz
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: gdanuser@scripps.edu.
Bokoch Gary M
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: bokoch@scripps.edu.
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Article Info
Journal
Developmental cell
Abbr.
Dev Cell
ISSN
1534-5807
DOI
10.1016/j.devcel.2007.08.011
Email
gdanuser@scripps.edu
bokoch@scripps.edu
Published
2007-11-00
Pages
646-662
Language
English
Region
United States
NLM ID
101120028
PMCID
PMC2170459
Subset
IM
Grants
NIGMS NIH HHS · GM44428 · United States
NIGMS NIH HHS · U01 GM067230 · United States
NIGMS NIH HHS · GM39434 · United States
NIGMS NIH HHS · R01 GM071868 · United States
NIGMS NIH HHS · R01 GM044428 · United States
NIGMS NIH HHS · U54 GM064346 · United States
NIGMS NIH HHS · R01 GM039434 · United States
NIGMS NIH HHS · R01 GM067230 · United States
NIGMS NIH HHS · U54 GM64346 · United States
NIGMS NIH HHS · GM67230 · United States
NIGMS NIH HHS · R01 GM071868-02 · United States
NIGMS NIH HHS · R01 GM039434-20 · United States
NIGMS NIH HHS · R01 GM044428-17 · United States
External Links
PubMed source DOI: 10.1016/j.devcel.2007.08.011 PMC Full Text View journal details
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