Published online January 2, 2007
doi:10.1083/jcb.200605099
The Journal of Cell Biology, Vol. 176, No. 1, 11-17
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Blasius et al.
Two binding partners cooperate to activate the molecular motor Kinesin-1
T. Lynne Blasius1,
Dawen Cai1,2,
Gloria T. Jih1,
Christopher P. Toret3, and
Kristen J. Verhey1
1 Department of Cell Biology and 2 Biophysics Research Division, University of Michigan, Ann Arbor, MI 48109
3 Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720
Correspondence to Kristen J. Verhey: kjverhey{at}umich.edu
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 
1 (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.
Abbreviations used in this paper: AMPPNP, 5'-adenylylimidodiphosphate; FEZ, fasciculation and elongation protein ; FP, fluorescent protein; IRES, internal ribosome entry site; JIP, JNK-interacting protein; KHC, kinesin heavy chain; KLC, kinesin light chain; MT, microtubule.
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