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© The Rockefeller University Press, 0021-9525/2001//959 $5.00
The Journal of Cell Biology, Volume 152, Number 5, , 2001 959-970

Cargo of Kinesin Identified as Jip Scaffolding Proteins and Associated Signaling Molecules

^a Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115
^b Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115
^c Howard Hughes Medical Institute, Department of Internal Medicine, and Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, Michigan 48109
Department of Cell Biology, Harvard Medical School, 240 Longwood Ave., Boston, MA 02115.(617) 432-1190(617) 432-1612

kverhey{at}hms.harvard.edu

The cargo that the molecular motor kinesin moves along microtubules has been elusive. We searched for binding partners of the COOH terminus of kinesin light chain, which contains tetratricopeptide repeat (TPR) motifs. Three proteins were found, the c-jun NH₂-terminal kinase (JNK)–interacting proteins (JIPs) JIP-1, JIP-2, and JIP-3, which are scaffolding proteins for the JNK signaling pathway. Concentration of JIPs in nerve terminals requires kinesin, as evident from the analysis of JIP COOH-terminal mutants and dominant negative kinesin constructs. Coprecipitation experiments suggest that kinesin carries the JIP scaffolds preloaded with cytoplasmic (dual leucine zipper–bearing kinase) and transmembrane signaling molecules (the Reelin receptor, ApoER2). These results demonstrate a direct interaction between conventional kinesin and a cargo, indicate that motor proteins are linked to their membranous cargo via scaffolding proteins, and support a role for motor proteins in spatial regulation of signal transduction pathways.

Key Words: kinesin • molecular motors • scaffolding protein • JNK signaling • Reelin

© 2001 The Rockefeller University Press

B. Schnapp, Department of Cell Biology, Harvard Medical School, 240 Longwood Ave., Boston, MA 02115. Tel.: (617) 432-3818. E-mail:bschnapp{at}hms.harvard.edu

Abbreviations used in this paper: DLK, dual leucine zipper kinase; HA, hemagglutinin; JIP, JNK-interacting protein; JNK, c-jun NH₂-terminal kinase; KHC, kinesin heavy chain; KIF, kinesin family member; KLC, kinesin light chain; MAP, mitogen-activated kinase; MKK, MAP kinase kinase; MT, microtubule; PP5, protein phosphatase 5; TPR, tetratricopeptide repeat.

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• Daire, V., Giustiniani, J., Leroy-Gori, I., Quesnoit, M., Drevensek, S., Dimitrov, A., Perez, F., Pous, C. (2009). Kinesin-1 Regulates Microtubule Dynamics via a c-Jun N-terminal Kinase-dependent Mechanism. J. Biol. Chem. 284: 31992-32001 [Abstract] [Full Text]  
• Hollenbeck, P.J. (2001). Kinesin Delivers: Identifying Receptors for Motor Proteins. JCB 152: 25-28 [Full Text]  

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