Squeezing in a Meal: Myosin Functions in Phagocytosis

Abstract

Phagocytosis is a receptor-mediated, actin-dependent process of internalization of large extracellular particles, such as pathogens or apoptotic cells. Engulfment of phagocytic targets requires the activity of myosins, actin-dependent molecular motors, which perform a variety of functions at distinct steps during phagocytosis. By applying force to actin filaments, the plasma membrane, and intracellular proteins and organelles, myosins can generate contractility, directly regulate actin assembly to ensure proper phagocytic internalization, and translocate phagosomes or other cargo to appropriate cellular locations. Recent studies using engineered microenvironments and phagocytic targets have demonstrated how altering the actomyosin cytoskeleton affects phagocytic behavior. Here, we discuss how studies using genetic and biochemical manipulation of myosins, force measurement techniques, and live-cell imaging have advanced our understanding of how specific myosins function at individual steps of phagocytosis.

Keywords: actin; macrophage; myosins; phagocytosis.

Figure I.

Domain organization and overall structural features of myosin isoforms involved in phagocytosis. Each myosin heavy chain consists of an N-terminal motor domain, a neck domain that binds light chains, and a tail domain that can include coiled-coil motifs to promote dimerization (in myosins-II, -V, and -X), membrane-binding Pleckstrin homology domains (in myosins-I and -X), or protein interaction motifs that promote cargo binding specificity. TH1, tail homology 1; TH2, tail homology 2; PH, Pleckstrin homology; IQ, light chain binding IQ motif; SH3, Src Homology 3; MyTH4, Myosin Tail Homology 4; GAP, GTPase-accelerating protein. Redrawn from [112].

Figure II.

Schematic of the sequential steps of FcR-mediated phagocytosis and the specific myosin isoforms involved. Myosin-X mediated filopodia function in phagocytic target search and capture. Myosin-I (Myo1e/f) and -IX (Myo9b) enable productive actin assembly within the phagocytic cup, with myosin-II generated contractility at the base. Myosin-V (Myo5a) assists in anchoring the phagosome once internalized.