Amphiphysin IIm, a novel amphiphysin II isoform, is required for macrophage phagocytosis

Phagocytosis of pathogens by macrophages initiates the innate immune respon se, 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 is oform 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 membran e extension around the bound particles. We define a signaling cascade in wh ich P13K is required to recruit amphiphysin II to the phagosome, and amphip hysin II in turn recruits dynamin. Thus, amphiphysin II facilitates a criti cal initial step in host response to infection.