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A more recent version of this article appeared on April 1, 2002
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Submitted on October 12, 2001
Revised on December 10, 2001
Accepted on January 16, 2002
R mediated phagocytosis
1 MRC Laboratory for Molecular Cell Biology and Cell Biology Unit and Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom
* Corresponding author. E-mail address: e.caron{at}ic.ac.uk.
Phagocytosis is the process whereby cells direct the spatially localised, receptor driven engulfment of particulate materials. It proceeds via remodelling of the actin cytoskeleton and shares many of the core cytoskeletal components involved in adhesion and migration. Small GTPases of the Rho family have been widely implicated in co-ordinating actin dynamics in response to extracellular signals and during diverse cellular processes including phagocytosis, yet the mechanisms controlling their recruitment and activation are not known. We show here that in response to FcR ligation, the guanine nucleotide exchange factor Vav translocates to nascent phagosomes and catalyses GTP-loading on Rac, but not Cdc42. The Vav induced Rac activation proceeds independently of Cdc42 function suggesting distinct roles for each GTPase during engulfment. Moreover, inhibition of Vav exchange activity or of Cdc42 activity does not prevent Rac recruitment to sites of particle attachment. We conclude that Rac is recruited to Fc membrane receptors in its inactive, GDP-bound state and that Vav regulates phagocytosis through subsequent catalysis of GDP/GTP exchange on Rac.
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