title: Role of phosphatidylinositol(4,5)bisphosphate organization in membrane transport by the Unc104 kinesin motor.
abstract: Unc104 (KIF1A) kinesin transports membrane vesicles along microtubules in lower and higher eukaryotes. Using an in vitro motility assay, we show that Unc104 uses a lipid binding pleckstrin homology (PH) domain to dock onto membrane cargo. Through its PH domain, Unc104 can transport phosphatidylinositol(4,5)bisphosphate (PtdIns(4,5)P2)-containing liposomes with similar properties to native vesicles. Interestingly, liposome movement by monomeric Unc104 motors shows a very steep dependence on PtdIns(4,5)P2 concentration (Hill coefficient of approximately 20), even though liposome binding is noncooperative. This switch-like transition for movement can be shifted to lower PtdIns(4,5)P2 concentrations by the addition of cholesterol/sphingomyelin or GM1 ganglioside/cholera toxin, conditions that produce raft-like behavior of Unc104 bound to lipid bilayers. These studies suggest that clustering of Unc104 in PtdIns(4,5)P2-containing rafts provides a trigger for membrane transport.
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 513 Parnassus Avenue, 94143, USA.
authors.forename: Dieter R
authors.initials: DR
authors.lastname: Klopfenstein
authors.forename: Michio
authors.initials: M
authors.lastname: Tomishige
authors.forename: Nico
authors.initials: N
authors.lastname: Stuurman
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Vale
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004023:Dictyostelium; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D016547:Kinesins / Q000302:isolation & purification / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism; D008870:Microtubules / Q000502:physiology; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000302:isolation & purification / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism / Q000502:physiology*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D022161:Transport Vesicles / Q000502:physiology*
chemical_list: D001798:Blood Proteins; D008051:Lipid Bilayers; D008081:Liposomes; D009419:Nerve Tissue Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D010750:Phosphoproteins; C039077:platelet protein P47; D016547:Kinesins