title: Two binding partners cooperate to activate the molecular motor Kinesin-1.
abstract: The regulation of molecular motors is an important cellular problem, as motility in the absence of cargo results in futile adenosine triphosphate hydrolysis. When not transporting cargo, the microtubule (MT)-based motor Kinesin-1 is kept inactive as a result of a folded conformation that allows autoinhibition of the N-terminal motor by the C-terminal tail. The simplest model of Kinesin-1 activation posits that cargo binding to nonmotor regions relieves autoinhibition. In this study, we show that binding of the c-Jun N-terminal kinase-interacting protein 1 (JIP1) cargo protein is not sufficient to activate Kinesin-1. Because two regions of the Kinesin-1 tail are required for autoinhibition, we searched for a second molecule that contributes to activation of the motor. We identified fasciculation and elongation protein zeta1 (FEZ1) as a binding partner of kinesin heavy chain. We show that binding of JIP1 and FEZ1 to Kinesin-1 is sufficient to activate the motor for MT binding and motility. These results provide the first demonstration of the activation of a MT-based motor by cellular binding partners.
authors.affiliation: Department of Cell Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: T Lynne
authors.initials: TL
authors.lastname: Blasius
authors.forename: Dawen
authors.initials: D
authors.lastname: Cai
authors.forename: Gloria T
authors.initials: GT
authors.lastname: Jih
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Toret
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Verhey
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002470:Cell Survival; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D005799:Genes, Dominant; D006801:Humans; D016547:Kinesins / Q000737:chemistry / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D011485:Protein Binding; D021381:Protein Transport; D051381:Rats; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C528597:FEZ1 protein, human; C118711:LZTS1 protein, human; C490666:MAPK8IP1 protein, human; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D025521:Tumor Suppressor Proteins; D016547:Kinesins