Cargo of Kinesin Identified As JIP Scaffolding Proteins and Associated Signaling Molecules

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2001 Mar 10

PMID 11238452

Citations 222

Authors

K J Verhey

D Meyer

R Deehan

J Blenis

B J Schnapp

T A Rapoport

B Margolis

Affiliations

Soon will be listed here.

Abstract

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 NH(2)-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.

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References

Bothwell M, Giniger E . Alzheimer's disease: neurodevelopment converges with neurodegeneration. Cell. 2000; 102(3):271-3. DOI: 10.1016/s0092-8674(00)00032-5. View

Brendza R, Serbus L, Duffy J, Saxton W . A function for kinesin I in the posterior transport of oskar mRNA and Staufen protein. Science. 2000; 289(5487):2120-2. PMC: 1764218. DOI: 10.1126/science.289.5487.2120. View

Terada S, Kinjo M, Hirokawa N . Oligomeric tubulin in large transporting complex is transported via kinesin in squid giant axons. Cell. 2000; 103(1):141-55. DOI: 10.1016/s0092-8674(00)00094-5. View

Jordan J, Landau E, Iyengar R . Signaling networks: the origins of cellular multitasking. Cell. 2000; 103(2):193-200. PMC: 3619409. DOI: 10.1016/s0092-8674(00)00112-4. View

Schlessinger J . Cell signaling by receptor tyrosine kinases. Cell. 2000; 103(2):211-25. DOI: 10.1016/s0092-8674(00)00114-8. View

Davis R . Signal transduction by the JNK group of MAP kinases. Cell. 2000; 103(2):239-52. DOI: 10.1016/s0092-8674(00)00116-1. View

Bowman A, Kamal A, Ritchings B, Philp A, McGrail M, Gindhart J . Kinesin-dependent axonal transport is mediated by the sunday driver (SYD) protein. Cell. 2000; 103(4):583-94. DOI: 10.1016/s0092-8674(00)00162-8. View

Saxton W, Hicks J, Goldstein L, Raff E . Kinesin heavy chain is essential for viability and neuromuscular functions in Drosophila, but mutants show no defects in mitosis. Cell. 1991; 64(6):1093-102. DOI: 10.1016/0092-8674(91)90264-y. View

Gho M, McDonald K, Ganetzky B, Saxton W . Effects of kinesin mutations on neuronal functions. Science. 1992; 258(5080):313-6. PMC: 3203545. DOI: 10.1126/science.1384131. View

10.

Yorifuji H, Inagaki M, Hirokawa N . The phosphorylation of kinesin regulates its binding to synaptic vesicles. J Biol Chem. 1992; 267(33):23930-6. View

11.

Hollenbeck P . Phosphorylation of neuronal kinesin heavy and light chains in vivo. J Neurochem. 1993; 60(6):2265-75. DOI: 10.1111/j.1471-4159.1993.tb03513.x. View

12.

Matthies H, Miller R, Palfrey H . Calmodulin binding to and cAMP-dependent phosphorylation of kinesin light chains modulate kinesin ATPase activity. J Biol Chem. 1993; 268(15):11176-87. View

13.

Gauger A, Goldstein L . The Drosophila kinesin light chain. Primary structure and interaction with kinesin heavy chain. J Biol Chem. 1993; 268(18):13657-66. View

14.

Patel N, Mancillas J . Cloning by insertional mutagenesis of a cDNA encoding Caenorhabditis elegans kinesin heavy chain. Proc Natl Acad Sci U S A. 1993; 90(19):9181-5. PMC: 47526. DOI: 10.1073/pnas.90.19.9181. View

15.

Skoufias D, Cole D, Wedaman K, Scholey J . The carboxyl-terminal domain of kinesin heavy chain is important for membrane binding. J Biol Chem. 1994; 269(2):1477-85. View

16.

McIlvain Jr J, Burkhardt J, Hamm-Alvarez S, Argon Y, Sheetz M . Regulation of kinesin activity by phosphorylation of kinesin-associated proteins. J Biol Chem. 1994; 269(29):19176-82. View

17.

Holzman L, Merritt S, Fan G . Identification, molecular cloning, and characterization of dual leucine zipper bearing kinase. A novel serine/threonine protein kinase that defines a second subfamily of mixed lineage kinases. J Biol Chem. 1994; 269(49):30808-17. View

18.

Lee K, Hollenbeck P . Phosphorylation of kinesin in vivo correlates with organelle association and neurite outgrowth. J Biol Chem. 1995; 270(10):5600-5. DOI: 10.1074/jbc.270.10.5600. View

19.

Terlecky S, Nuttley W, McCollum D, Sock E, Subramani S . The Pichia pastoris peroxisomal protein PAS8p is the receptor for the C-terminal tripeptide peroxisomal targeting signal. EMBO J. 1995; 14(15):3627-34. PMC: 394437. DOI: 10.1002/j.1460-2075.1995.tb00032.x. View

20.

Steinberg G, Schliwa M . The Neurospora organelle motor: a distant relative of conventional kinesin with unconventional properties. Mol Biol Cell. 1995; 6(11):1605-18. PMC: 301314. DOI: 10.1091/mbc.6.11.1605. View