Blasius T Lynne, Cai Dawen, Jih Gloria T, Toret Christopher P, Verhey Kristen J
Department of Cell Biology, University of Michigan, Ann Arbor, MI 48109, USA.
J Cell Biol. 2007 Jan 1;176(1):11-7. doi: 10.1083/jcb.200605099.
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.
分子马达的调控是一个重要的细胞问题，因为在没有货物的情况下运动性会导致三磷酸腺苷的无效水解。当不运输货物时，基于微管（MT）的马达驱动蛋白-1由于折叠构象而保持无活性，这种构象允许C末端尾巴对N末端马达进行自抑制。驱动蛋白-1激活的最简单模型认为，货物与非马达区域的结合可解除自抑制。在本研究中，我们表明c-Jun N末端激酶相互作用蛋白1（JIP1）货物蛋白的结合不足以激活驱动蛋白-1。由于驱动蛋白-1尾巴的两个区域是自抑制所必需的，我们寻找了第二个有助于激活该马达的分子。我们鉴定出成束和延伸蛋白zeta1（FEZ1）是驱动蛋白重链的结合伴侣。我们表明JIP1和FEZ1与驱动蛋白-1的结合足以激活该马达以实现微管结合和运动。这些结果首次证明了细胞结合伴侣对基于微管的马达的激活作用。
