Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules.
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.
Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. kverhey@hms.harvard.edu
K J
KJ
Verhey
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D
Meyer
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R
Deehan
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J
Blenis
B J
BJ
Schnapp
T A
TA
Rapoport
B
B
Margolis
D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D016547:Kinesins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D026502:LDL-Receptor Related Proteins; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D051381:Rats; D018110:Receptors, Lipoprotein / Q000378:metabolism; D000091042:Reelin Protein; D016415:Sequence Alignment; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D026502:LDL-Receptor Related Proteins; C490666:MAPK8IP1 protein, human; C408376:MAPK8IP2 protein, human; C485750:MAPK8IP3 protein, human; C490665:Mapk8ip protein, mouse; C110528:Mapk8ip1 protein, rat; C486564:Mapk8ip2 protein, mouse; C403619:Mapk8ip3 protein, mouse; D020409:Molecular Motor Proteins; D009419:Nerve Tissue Proteins; D018110:Receptors, Lipoprotein; D000091042:Reelin Protein; C000717129:Reln protein, rat; C098773:low density lipoprotein receptor-related protein 8; D020930:MAP Kinase Kinase Kinases; C090757:mitogen-activated protein kinase kinase kinase 12; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D016547:Kinesins