Myosin I Links PIP3 Signaling to Remodeling of the Actin Cytoskeleton in Chemotaxis

A subset of myosin motor proteins binds the membrane phospholipid PIP3 to link membrane and cytoskeletal dynamics. Linking Membrane Lipids to Cytoskeletal Dynamics The phospholipid PIP3 (phosphatidylinositol 3,4,5-trisphosphate) can be generated at the plasma membrane in cells orienting their movement according to an external chemical gradient (a process called chemotaxis) or in cells engulfing particles or other cells (a process called phagocytosis). Both chemotaxis and phagocytosis require reorganization of the cytoskeleton. Various type I myosin isoforms (specifically, ID, IE, and IF) are motor proteins that interact with the actin cytoskeleton as PIP3-binding proteins. Here, Chen et al. showed that myosins ID, IE, and IF were required for PIP3-induced changes in the cytoskeleton. Dictyostelium cells lacking these three myosin I isoforms showed defects in chemotaxis and in phagocytosis of yeast cells. Furthermore, these mutant Dictyostelium cells failed to remodel the cytoskeleton in response to a chemoattractant. Thus, specific myosin I isoforms couple stimuli that generate PIP3 to changes in the cytoskeleton during chemotaxis and phagocytosis. Class I myosins participate in various interactions between the cell membrane and the cytoskeleton. Several class I myosins preferentially bind to acidic phospholipids, such as phosphatidylserine and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], through a tail homology 1 (TH1) domain. Here, we show that the second messenger lipid phosphatidylinositol 3,4,5-trisphosphate (PIP3) binds to the TH1 domain of a subset of Dictyostelium class I myosins (ID, IE, and IF) and recruits them to the plasma membrane. The PIP3-regulated membrane recruitment of myosin I promoted chemotaxis and induced chemoattractant-stimulated actin polymerization. Similarly, PIP3 recruited human myosin IF to the plasma membrane upon chemotactic stimulation in a neutrophil cell line. These data suggest a mechanism through which the PIP3 signal is transmitted through myosin I to the actin cytoskeleton.

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