The motor protein myosin 1G functions in FcγR-mediated phagocytosis.

Phagocytosis is the force-dependent complex cellular process by which immune cells engulf particles. Although there has been considerable progress in understanding ligand-receptor-induced actin polymerisation in pushing the membrane around the particle, significantly less is known about how localised contractile activities regulate cup closure in coordination with the actin cytoskeleton. Herein, we show that the unconventional class-I myosin, myosin 1G (Myo1G) is localised at phagocytic cups following Fcγ-receptor (FcγR) ligation in macrophages. This progressive recruitment is dependent on the activity of phosphoinositide 3-kinase and is particularly important for engulfment of large particles. Furthermore, point mutations in the conserved pleckstrin homology-like domain of Myo1G abolishes the localisation of the motor protein at phagocytic cups and inhibits engulfment downstream of FcγR. Binding of Myo1G to both F-actin and phospholipids might enable cells to transport phospholipids towards the leading edge of cups and to facilitate localised contraction for cup closure.