Myosin-X, a novel myosin with pleckstrin homology domains, associates withregions of dynamic actin

Myosin-X is the founding member of a novel class of unconventional myosins characterized by a tail domain containing multiple pleckstrin homology doma ins, We report here the full-length cDNA sequences of human and bovine myos in-X as well as the first characterization of this protein's distribution a nd biochemical properties. The 235 kDa myosin-X contains a head domain with <45% protein sequence identity to other myosins, three IQ motifs, and a pr edicted stalk of coiled coil. Like several other unconventional myosins and a plant kinesin, myosin-X contains both a myosin tail homology 4 (MyTH4) d omain and a FERM (band 4.1/ezrin/radixin/moesin) domain. The unique tail do main also includes three pleckstrin homology domains, which have been impli cated in phosphatidylinositol phospholipid signaling, and three PEST sites, which may allow cleavage of the myosin tail. Most intriguingly, myosin-X i n cultured cells is present at the edges of lamellipodia, membrane ruffles, and the tips of filopodial actin bundles. The tail domain structure, bioch emical features, and localization of myosin-X suggest that this novel uncon ventional myosin plays a role in regions of dynamic actin.