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.

Annotation

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