Amphiphysin IIm, a novel amphiphysin II isoform, is required for macrophage phagocytosis.
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.
Gold
E S
ES
Department of Immunology, University of Washington, Seattle 98159, USA.
Morrissette
N S
NS
Underhill
D M
DM
Guo
J
J
Bassetti
M
M
Aderem
A
A
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
D000911:Antibodies, Monoclonal; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C075637:amphiphysin; D019869:Phosphatidylinositol 3-Kinases; D020558:GTP Phosphohydrolases; D034281:Dynamins