title: Amphiphysin IIm, a novel amphiphysin II isoform, is required for macrophage phagocytosis.
abstract: Phagocytosis of pathogens by macrophages initiates the innate immune response, which in turn orchestrates the adaptive immune response. Amphiphysin II participates in receptor-mediated endocytosis, in part, by recruiting the GTPase dynamin to the nascent endosome. We demonstrate here that a novel isoform of amphiphysin II associates with early phagosomes in macrophages. We have ablated the dynamin-binding site of this protein and shown that this mutant form of amphiphysin II inhibits phagocytosis at the stage of membrane extension around the bound particles. We define a signaling cascade in which PI3K is required to recruit amphiphysin II to the phagosome, and amphiphysin II in turn recruits dynamin. Thus, amphiphysin II facilitates a critical initial step in host response to infection.
authors.affiliation: Department of Immunology, University of Washington, Seattle 98159, USA.
authors.forename: E S
authors.initials: ES
authors.lastname: Gold
authors.forename: N S
authors.initials: NS
authors.lastname: Morrissette
authors.forename: D M
authors.initials: DM
authors.lastname: Underhill
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.forename: M
authors.initials: M
authors.lastname: Bassetti
authors.forename: A
authors.initials: A
authors.lastname: Aderem
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001665:Binding Sites; D019556:COS Cells; D034281:Dynamins; D004705:Endocytosis / Q000276:immunology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D010587:Phagocytosis / Q000276:immunology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D018909:src Homology Domains
chemical_list: D000911:Antibodies, Monoclonal; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C075637:amphiphysin; D019869:Phosphatidylinositol 3-Kinases; D020558:GTP Phosphohydrolases; D034281:Dynamins