Coatomer-bound Cdc42 regulates dynein recruitment to COPI vesicles.
Cytoskeletal dynamics at the Golgi apparatus are regulated in part through a binding interaction between the Golgi-vesicle coat protein, coatomer, and the regulatory GTP-binding protein Cdc42 (Wu, W.J., J.W. Erickson, R. Lin, and R.A. Cerione. 2000. Nature. 405:800-804; Fucini, R.V., J.L. Chen, C. Sharma, M.M. Kessels, and M. Stamnes. 2002. Mol. Biol. Cell. 13:621-631). The precise role of this complex has not been determined. We have analyzed the protein composition of Golgi-derived coat protomer I (COPI)-coated vesicles after activating or inhibiting signaling through coatomer-bound Cdc42. We show that Cdc42 has profound effects on the recruitment of dynein to COPI vesicles. Cdc42, when bound to coatomer, inhibits dynein binding to COPI vesicles whereas preventing the coatomer-Cdc42 interaction stimulates dynein binding. Dynein recruitment was found to involve actin dynamics and dynactin. Reclustering of nocodazole-dispersed Golgi stacks and microtubule/dynein-dependent ER-to-Golgi transport are both sensitive to disrupting Cdc42 mediated signaling. By contrast, dynein-independent transport to the Golgi complex is insensitive to mutant Cdc42. We propose a model for how proper temporal regulation of motor-based vesicle translocation could be coupled to the completion of vesicle formation.
Chen
Ji-Long
JL
Department of Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA.
Fucini
Raymond V
RV
Lacomis
Lynne
L
Erdjument-Bromage
Hediye
H
Tempst
Paul
P
Stamnes
Mark
M
D000199:Actins / Q000378:metabolism; D000818:Animals; D022181:COP-Coated Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D002417:Cattle; D002522:Chlorocebus aethiops; D020756:Coatomer Protein / Q000378:metabolism*; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D025461:Feedback, Physiological / Q000502:physiology; D006056:Golgi Apparatus / Q000378:metabolism / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D009154:Mutation / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D013347:Subcellular Fractions; D014709:Vero Cells; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D020756:Coatomer Protein; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D004398:Dyneins; D020764:cdc42 GTP-Binding Protein