Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 1516K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Blasius, T. L. Articles by Verhey, K. J. Search for Related Content PubMed PubMed Citation Articles by Blasius, T. L. Articles by Verhey, K. J. Related Collections Related Articles Social Bookmarking                            What's this?

Two binding partners cooperate to activate the molecular motor Kinesin-1

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.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Articles

Partners in kinesin activation

Nicole LeBrasseur
J. Cell Biol. 2007 176: 2. [Full Text] [PDF]

This article has been cited by other articles:

• Haedicke, J., Brown, C., Naghavi, M. H. (2009). The brain-specific factor FEZ1 is a determinant of neuronal susceptibility to HIV-1 infection. Proc. Natl. Acad. Sci. USA 106: 14040-14045 [Abstract] [Full Text]  
• Ittner, L. M., Ke, Y. D., Gotz, J. (2009). Phosphorylated Tau Interacts with c-Jun N-terminal Kinase-interacting Protein 1 (JIP1) in Alzheimer Disease. J. Biol. Chem. 284: 20909-20916 [Abstract] [Full Text]  
• Vinogradova, M. V., Malanina, G. G., Reddy, A. S. N., Fletterick, R. J. (2009). Structure of the complex of a mitotic kinesin with its calcium binding regulator. Proc. Natl. Acad. Sci. USA 106: 8175-8179 [Abstract] [Full Text]  
• Toda, H., Mochizuki, H., Flores, R. III, Josowitz, R., Krasieva, T. B., LaMorte, V. J., Suzuki, E., Gindhart, J. G., Furukubo-Tokunaga, K., Tomoda, T. (2008). UNC-51/ATG1 kinase regulates axonal transport by mediating motor-cargo assembly. Genes Dev. 22: 3292-3307 [Abstract] [Full Text]  
• Schonteich, E., Wilson, G. M., Burden, J., Hopkins, C. R., Anderson, K., Goldenring, J. R., Prekeris, R. (2008). The Rip11/Rab11-FIP5 and kinesin II complex regulates endocytic protein recycling. J. Cell Sci. 121: 3824-3833 [Abstract] [Full Text]  
• Hirokawa, N., Noda, Y. (2008). Intracellular Transport and Kinesin Superfamily Proteins, KIFs: Structure, Function, and Dynamics. Physiol. Rev. 88: 1089-1118 [Abstract] [Full Text]  
• Dietrich, K. A., Sindelar, C. V., Brewer, P. D., Downing, K. H., Cremo, C. R., Rice, S. E. (2008). The kinesin-1 motor protein is regulated by a direct interaction of its head and tail. Proc. Natl. Acad. Sci. USA 105: 8938-8943 [Abstract] [Full Text]  
• Hackney, D. D. (2007). Jump-starting kinesin. JCB 176: 7-9 [Abstract] [Full Text]  
• Cai, D., Hoppe, A. D., Swanson, J. A., Verhey, K. J. (2007). Kinesin-1 structural organization and conformational changes revealed by FRET stoichiometry in live cells. JCB 176: 51-63 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents