RGD Reference Report - Rap1 activation is required for Fc gamma receptor-dependent phagocytosis. - Rat Genome Database

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

Authors: Chung, J  Serezani, CH  Huang, SK  Stern, JN  Keskin, DB  Jagirdar, R  Brock, TG  Aronoff, DM  Peters-Golden, M 
Citation: Chung J, etal., J Immunol. 2008 Oct 15;181(8):5501-9.
RGD ID: 9835043
Pubmed: (View Article at PubMed) PMID:18832707

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.


Gene Ontology Annotations    

Biological Process

Cellular Component

Objects Annotated

Genes (Rattus norvegicus)
Rap1a  (RAP1A, member of RAS oncogene family)
Rapgef1  (Rap guanine nucleotide exchange factor 1)

Additional Information