Membrane-cytoskeleton mechanical feedback mediated by myosin-I controls phagocytic efficiency

Abstract

Phagocytosis of invading pathogens or cellular debris requires a dramatic change in cell shape driven by actin polymerization. For antibody-covered targets, phagocytosis is thought to proceed through the sequential engagement of Fc-receptors on the phagocyte with antibodies on the target surface, leading to the extension and closure of the phagocytic cup around the target. We have found that two actin-dependent molecular motors, class 1 myosins myosin 1e and myosin 1f, are specifically localized to Fc-receptor adhesions and required for efficient phagocytosis of antibody-opsonized targets. Using primary macrophages lacking both myosin 1e and myosin 1f, we found that without the actin-membrane linkage mediated by these myosins, the organization of individual adhesions is compromised, leading to excessive actin polymerization, slower adhesion turnover, and deficient phagocytic internalization. This work identifies a novel role for class 1 myosins in coordinated adhesion turnover during phagocytosis and supports a model for a membrane-tension based feedback mechanism for phagocytic cup closure.

Human Myosin 1e tail but not motor domain replaces fission yeast Myo1 domains to support myosin-I function during endocytosis

“…"Long-tailed" class I myosins of similar structure also exist in lower eukaryotes, such as yeast, Dictyostelium, and Acanthamoeba, and are proposed to be the evolutionary ancestor of all common myosins (2). In both unicellular and multicellular organisms, long-tailed class I myosins seem to function in similar physiological processes, including clathrin-mediated endocytosis, pinocytosis, and phagocytosis (3)(4)(5)(6)(7)(8)(9)(10). Moreover, these myosins have similar binding partners and even appear at the same stage during endocytosis in diverse organisms.…”