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 find 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 find 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 role for class 1 myosins in coordinated adhesion turnover during phagocytosis and supports a mechanism involving membrane-cytoskeletal crosstalk for phagocytic cup closure.
Highlights
Phagocytosis of invading pathogens or cellular debris requires a dramatic change in cell shape driven by actin polymerization
We report that two class 1 myosins, myosin 1e and myosin 1f, small monomeric actin-based motors that can bind to the actin cytoskeleton through their motor domains and the plasma membrane through their tails, are associated with Fc-receptor adhesions and control membrane tension and organization at these sites throughout phagocytosis
Using a myo1e/f double knockout mouse model, we find that macrophages lacking these myosins assemble phagocytic cups of clumped and disorganized actin, exhibit slower Fcγ receptors (FcRs) adhesion turnover and, as a result, are deficient at internalizing targets
Summary
Phagocytosis of invading pathogens or cellular debris requires a dramatic change in cell shape driven by actin polymerization. Over the course of phagocytosis, macrophages experience a steep increase in membrane tension, which triggers exocytosis of intracellular membrane stores that increase cell surface area for internalization[9]. It is unknown how or if this change in membrane tension affects the actin assembly required for phagocytic cup closure. The longstanding model of phagocytic cup closure involves Factin assembly at discrete FcR adhesions between the phagocyte and the IgG-coated particle, with subsequent cup extension driven by the formation of additional Fc receptor-IgG bonds in a zipper-like fashion along the target[10]. This work describes a biophysical component precisely controlling actin dynamics to promote extension and closure of the phagocytic cup
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