title: Phospholipid-dependent regulation of the motor activity of myosin X.
abstract: Myosin X is involved in the reorganization of the actin cytoskeleton and protrusion of filopodia. Here we studied the molecular mechanism by which bovine myosin X is regulated. The globular tail domain inhibited the motor activity of myosin X in a Ca(2+)-independent manner. Structural analysis revealed that myosin X is monomeric and that the band 4.1-ezrin-radixin-moesin (FERM) and pleckstrin homology (PH) domains bind to the head intramolecularly, forming an inhibited conformation. Binding of phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P(3)) to the PH domain reversed the tail-induced inhibition and induced the formation of myosin X dimers. Consistently, disruption of the binding of PtdIns(3,4,5)P(3) attenuated the translocation of myosin X to filopodial tips in cells. We propose the following mechanism: first, the tail inhibits the motor activity of myosin X by intramolecular head-tail interactions to form the folded conformation; second, phospholipid binding reverses the inhibition and disrupts the folded conformation, which induces dimer formation, thereby activating the mechanical and cargo transporter activity of myosin X.
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Umeki
authors.forename: Hyun Suk
authors.initials: HS
authors.lastname: Jung
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sakai
authors.forename: Osamu
authors.initials: O
authors.lastname: Sato
authors.forename: Reiko
authors.initials: R
authors.lastname: Ikebe
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Ikebe
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002417:Cattle; D019281:Dimerization; D009218:Myosins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000502:physiology; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D017510:Protein Folding; D017434:Protein Structure, Tertiary
chemical_list: D018129:Phosphatidylinositol Phosphates; C060974:phosphatidylinositol 3,4,5-triphosphate; D009218:Myosins