RhoG is required for both Fc gamma R- and CR3-mediated phagocytosis
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Published version
Author(s)
Tzircotis, George
Braga, Vania MM
Caron, Emmanuelle
Type
Journal Article
Abstract
Phagocytosis is a highly ordered process orchestrated by signalling through Rho GTPases to locally organise the actin cytoskeleton and drive particle uptake. Specific Rho family members that regulate phagocytosis are not known, as the majority of studies have relied on the use of dominant-negative mutants and/or toxins, which can inactivate multiple Rho GTPases. To identify the relevant GTPases for phagocytosis through the Fcγ receptor (FcγR) and complement receptor 3 (CR3), we depleted 20 Rho proteins individually in an RNA interference (RNAi) screen. We find that distinct GTPase subsets are required for actin polymerisation and uptake by macrophages: FcγR-dependent engulfment requires Cdc42 and Rac2 (but not Rac1), whereas CR3 requires RhoA. Surprisingly, RhoG is required for particle uptake through both FcγR and CR3. RhoG has been previously linked to Rac and Cdc42 signalling in different model systems, but not to RhoA. Interestingly, we find that RhoG is also recruited and activated at phagocytic cups downstream of FcγR and CR3, irrespective of their distinct actin structures and mechanisms of internalisation. Thus, the functional links between RhoG and RhoA downstream of CR3-dependent phagocytosis are new and unexpected. Our data suggest a broad role for RhoG in consolidating signals from multiple receptors during phagocytosis.
Date Issued
2011-09-01
Date Acceptance
2011-03-08
Citation
JOURNAL OF CELL SCIENCE, 2011, 124 (17), pp.2897-2902
ISSN
0021-9533
Publisher
COMPANY OF BIOLOGISTS LTD
Start Page
2897
End Page
2902
Journal / Book Title
JOURNAL OF CELL SCIENCE
Volume
124
Issue
17
Copyright Statement
© 2011 Published by The Company of Biologists Ltd
Sponsor
Biotechnology and Biological Sciences Research Council (BBSRC)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000294419200003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
BB/D019400/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
CR3
Fc gamma R
Macrophage
Phagocytosis
Small GTPases
APOPTOTIC CELLS
GTPASE RHOG
NEURITE OUTGROWTH
LIVE CELLS
RAC1
ACTIVATION
INTEGRIN
CDC42
MACROPHAGES
MECHANISMS
Publication Status
Published
Date Publish Online
2011-08-30