Cofilin Activity Downstream of Pak1 Regulates Cell Protrusion Efficiency by Organizing Lamellipodium and Lamella Actin Networks

Violaine Delorme, Matthias Machacek, Céline DerMardirossian, Karen L. Anderson, Torsten Wittmann, Dorit Hanein, Clare Waterman-Storer, Gaudenz Danuser, Gary M. Bokoch

Research output: Contribution to journalArticle

129 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)646-662
Number of pages17
JournalDevelopmental Cell
Volume13
Issue number5
DOIs
Publication statusPublished - Nov 6 2007

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Keywords

  • CELLBIO

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Delorme, V., Machacek, M., DerMardirossian, C., Anderson, K. L., Wittmann, T., Hanein, D., ... Bokoch, G. M. (2007). Cofilin Activity Downstream of Pak1 Regulates Cell Protrusion Efficiency by Organizing Lamellipodium and Lamella Actin Networks. Developmental Cell, 13(5), 646-662. https://doi.org/10.1016/j.devcel.2007.08.011