Rap1 activation is required for Fc gamma receptor-dependent phagocytosis.

Chung J, Serezani CH, Huang SK, Stern JN, Keskin DB, Jagirdar R, Brock TG, Aronoff DM, Peters-Golden M
J Immunol. 2008 181 (8): 5501-9

PMID: 18832707 · PMCID: PMC3077557 · DOI:10.4049/jimmunol.181.8.5501

Phagocytosis of IgG-opsonized microbes via the Fc gamma receptor (Fc gammaR) requires the precise coordination of a number of signaling molecules, including the low-molecular mass GTPases. Little is known about the Ras-family GTPase Rap1 in this process. We therefore investigated its importance in mediating Fc gammaR-dependent phagocytosis in NR8383 rat alveolar macrophages. Pulldown of active Rap1 and fluorescence microscopic analysis of GFP-RalGDS (Ral guanine dissociation stimulator)-transfected macrophages revealed that Rap1 is indeed activated by Fc gammaR crosslinking. Inhibition of Rap1 activity, both by Rap1GAP (GTPase-activating protein) expression and liposome-delivered blocking Ab, severely impaired the ability of cells to ingest IgG-opsonized targets. Fc gammaR-induced Rap1 activation was found to be independent of both cAMP and Ca(2+), suggesting a role for the second messenger-independent guanosine exchange factor, C3G. This was supported by the facts that 1) liposome-delivered blocking Ab against C3G inhibited both Fc gammaR-dependent phagocytosis and Rap1 activation, and 2) both active Rap1GTP and C3G were found to translocate to the phagosome. Taken together, our data demonstrate a novel role for Rap1 and its exchange factor C3G in mediating Fc gammaR-dependent phagocytosis.

MeSH Terms (14)

Animals Calcium Cyclic AMP Guanine Nucleotide-Releasing Factor 2 Humans Immunologic Capping Liposomes Macrophages, Alveolar Phagocytosis rap1 GTP-Binding Proteins Rats Receptors, IgG Second Messenger Systems U937 Cells

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