title: A role for mammalian diaphanous-related formins in complement receptor (CR3)-mediated phagocytosis in macrophages.
abstract: Macrophages, dendritic cells, and neutrophils use phagocytosis to capture and clear off invading pathogens. The process is triggered by the interaction of ligands on the pathogens' surface with specific phagocytic receptors, including immunoglobulin (FcR) and complement C3bi (CR3) receptors (integrin alpha(M)beta2, Mac1) . Localized actin-filament assembly that acts as the driving force for particle engulfment is controlled by Rho-family small GTPases . RhoA regulates CR3-mediated phagocytosis through a mechanism that is still unclear . Mammalian Diaphanous-related (mDia) formins participate in the generation of a diverse set of actin-remodeling events downstream of RhoA , and mDia1 is recruited around fibronectin-coated beads in a RhoA-dependent manner in fibroblasts . Here, we set out to examine whether mDia proteins are involved in CR3-mediated phagocytosis in macrophages. We show that the RhoA effector mDia1 is recruited early during CR3-mediated phagocytosis and colocalizes with polymerized actin in the phagocytic cup. Interfering with mDia activity inhibits CR3-mediated phagocytosis while having no effect on FcR-mediated phagocytosis. These results indicate a new function for mDia proteins in the regulation of actin polymerization during CR3-mediated phagocytosis.
authors.affiliation: Membrane and Cytoskeleton Dynamics Group, Unité mixte de recherche 144, Centre National de la Recherche Scientifique/Institut Curie, 75248 Paris, France.
authors.forename: Emma
authors.initials: E
authors.lastname: Colucci-Guyon
authors.forename: Florence
authors.initials: F
authors.lastname: Niedergang
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Wallar
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Alberts
authors.forename: Philippe
authors.initials: P
authors.lastname: Chavrier
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D000080865:Formins; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D008264:Macrophages / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008855:Microscopy, Electron, Scanning; D010587:Phagocytosis / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D000199:Actins; D002352:Carrier Proteins; C491464:Diap1 protein, mouse; D000080865:Formins; D016177:Macrophage-1 Antigen; D034741:RNA, Small Interfering