Spatial and Temporal Control of Cofilin Activity Is Required for Directional Sensing during Chemotaxis

Ghassan Mouneimne, Vera M. Desmarais, Mazen Sidani, Eliana Scemes, Weigang Wang, Xiaoyan Song, Robert J. Eddy, John S. Condeelis

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

Background: Previous work has led to the hypothesis that cofilin severing, as regulated by PLC, is involved in chemotactic sensing. We have tested this hypothesis by investigating whether activation of endogenous cofilin is spatially and temporally linked to sensing an EGF point source in carcinoma cells. Results: We demonstrate that inhibition of endogenous cofilin activity with either siRNA or overexpression of LIMK suppresses directional sensing in carcinoma cells. LIMK siRNA knockdown, which suppresses cofilin phosphorylation, and microinjection of S3C cofilin, a cofilin mutant that is constitutively active and not phosphorylated by LIMK, also inhibits directional sensing and chemotaxis. These results indicate that phosphorylation of cofilin by LIMK, in addition to cofilin activity, is required for chemotaxis. Cofilin activity concentrates rapidly at the newly formed leading edge facing the gradient, whereas cofilin phosphorylation increases throughout the cell. Quantification of these results indicates that the amplification of asymmetric actin polymerization required for protrusion toward the EGF gradient occurs at the level of cofilin but not at the level of PLC activation by EGFR. Conclusions: These results indicate that local activation of cofilin by PLC and its global inactivation by LIMK phosphorylation combine to generate the local asymmetry of actin polymerization required for chemotaxis.

Original languageEnglish (US)
Pages (from-to)2193-2205
Number of pages13
JournalCurrent Biology
Volume16
Issue number22
DOIs
StatePublished - Nov 21 2006

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Actin Depolymerizing Factors
chemotaxis
Chemotaxis
phosphorylation
small interfering RNA
polymerization
carcinoma
actin
Phosphorylation
cells
Programmable logic controllers
inactivation
concentrates
Chemical activation
Epidermal Growth Factor
Polymerization
mutants
Small Interfering RNA
Actins
Cells

Keywords

  • CELLBIO

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Spatial and Temporal Control of Cofilin Activity Is Required for Directional Sensing during Chemotaxis. / Mouneimne, Ghassan; Desmarais, Vera M.; Sidani, Mazen; Scemes, Eliana; Wang, Weigang; Song, Xiaoyan; Eddy, Robert J.; Condeelis, John S.

In: Current Biology, Vol. 16, No. 22, 21.11.2006, p. 2193-2205.

Research output: Contribution to journalArticle

Mouneimne, Ghassan ; Desmarais, Vera M. ; Sidani, Mazen ; Scemes, Eliana ; Wang, Weigang ; Song, Xiaoyan ; Eddy, Robert J. ; Condeelis, John S. / Spatial and Temporal Control of Cofilin Activity Is Required for Directional Sensing during Chemotaxis. In: Current Biology. 2006 ; Vol. 16, No. 22. pp. 2193-2205.
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