A WAVE2-Abi1 complex mediates CSF-1-induced F-actin-rich membrane protrusions and migration in macrophages

Wassim Abou Kheir, Jean Claude Gevrey, Hideki Yamaguchi, Beth Isaac, Dianne Cox

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Colony-stimulating factor 1 (CSF-1) is an important physiological chemoattractant for macrophages. The mechanisms by which CSF-1 elicits the formation of filamentous actin (F-actin)-rich membrane protrusions and induces macrophage migration are not fully understood. In particular, very little is known regarding the contribution of the different members of the Wiskott-Aldrich Syndrome protein (WASP) family of actin regulators in response to CSF-1. Although a role for WASP itself in macrophage chemotaxis has been previously identified, no data was available regarding the function of WASP family verprolin-homologous (WAVE) proteins in this cell type. We found that WAVE2 was the predominant isoform to be expressed in primary macrophages and in cells derived from the murine monocyte/macrophage RAW264.7 cell line (RAW/LR5). CSF-1 treatment of macrophages resulted in WAVE2 accumulation in F-actin-rich protrusions induced by CSF-1. Inhibition of WAVE2 function by expressing a dominant-negative mutant or introducing anti-WAVE2 antibodies in RAW/LR5 cells, as well as reduction of endogenous WAVE2 expression by RNA-mediated interference (RNAi), resulted in a significant reduction of CSF-1-elicited F-actin protrusions. WAVE2 was found in a protein complex together with Abelson kinase interactor 1 (Abi1) in resting or stimulated cells. Both WAVE2 and Abi1 were recruited to and necessary for the formation of F-actin protrusions in response to CSF-1. Reducing the levels of WAVE2, directly or by targeting Abi1, resulted in an impaired cell migration to CSF-1. Altogether these data identify a WAVE2-Abi1 complex crucial for the normal actin cytoskeleton reorganization and migration of macrophages in response to CSF-1.

Original languageEnglish (US)
Pages (from-to)5369-5379
Number of pages11
JournalJournal of Cell Science
Volume118
Issue number22
DOIs
StatePublished - Nov 15 2005

Fingerprint

Macrophage Colony-Stimulating Factor
Actins
Phosphotransferases
Macrophages
Membranes
Wiskott-Aldrich Syndrome Protein Family
Wiskott-Aldrich Syndrome Protein
Chemotactic Factors
Chemotaxis
RNA Interference
Actin Cytoskeleton
Cell Movement
Anti-Idiotypic Antibodies
Protein Isoforms
Proteins
Cell Line

Keywords

  • Abi1
  • Actin cytoskeleton
  • Cell migration
  • Macrophage
  • WAVE2

ASJC Scopus subject areas

  • Cell Biology

Cite this

A WAVE2-Abi1 complex mediates CSF-1-induced F-actin-rich membrane protrusions and migration in macrophages. / Kheir, Wassim Abou; Gevrey, Jean Claude; Yamaguchi, Hideki; Isaac, Beth; Cox, Dianne.

In: Journal of Cell Science, Vol. 118, No. 22, 15.11.2005, p. 5369-5379.

Research output: Contribution to journalArticle

Kheir, Wassim Abou ; Gevrey, Jean Claude ; Yamaguchi, Hideki ; Isaac, Beth ; Cox, Dianne. / A WAVE2-Abi1 complex mediates CSF-1-induced F-actin-rich membrane protrusions and migration in macrophages. In: Journal of Cell Science. 2005 ; Vol. 118, No. 22. pp. 5369-5379.
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AB - Colony-stimulating factor 1 (CSF-1) is an important physiological chemoattractant for macrophages. The mechanisms by which CSF-1 elicits the formation of filamentous actin (F-actin)-rich membrane protrusions and induces macrophage migration are not fully understood. In particular, very little is known regarding the contribution of the different members of the Wiskott-Aldrich Syndrome protein (WASP) family of actin regulators in response to CSF-1. Although a role for WASP itself in macrophage chemotaxis has been previously identified, no data was available regarding the function of WASP family verprolin-homologous (WAVE) proteins in this cell type. We found that WAVE2 was the predominant isoform to be expressed in primary macrophages and in cells derived from the murine monocyte/macrophage RAW264.7 cell line (RAW/LR5). CSF-1 treatment of macrophages resulted in WAVE2 accumulation in F-actin-rich protrusions induced by CSF-1. Inhibition of WAVE2 function by expressing a dominant-negative mutant or introducing anti-WAVE2 antibodies in RAW/LR5 cells, as well as reduction of endogenous WAVE2 expression by RNA-mediated interference (RNAi), resulted in a significant reduction of CSF-1-elicited F-actin protrusions. WAVE2 was found in a protein complex together with Abelson kinase interactor 1 (Abi1) in resting or stimulated cells. Both WAVE2 and Abi1 were recruited to and necessary for the formation of F-actin protrusions in response to CSF-1. Reducing the levels of WAVE2, directly or by targeting Abi1, resulted in an impaired cell migration to CSF-1. Altogether these data identify a WAVE2-Abi1 complex crucial for the normal actin cytoskeleton reorganization and migration of macrophages in response to CSF-1.

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