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Molecular and Cellular Biology, December 2001, p. 8022-8034, Vol. 21, No. 23
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.23.8022-8034.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Kinectin Is a Key Effector of RhoG Microtubule-Dependent Cellular Activity

E. Vignal,1 A. Blangy,1 M. Martin,2 C. Gauthier-Rouvière,1 and P. Fort1,*

Centre de Recherche en Biochimie Macromoléculaire, CNRS-UPR1086, 34293 Montpellier cedex 5,1 and Laboratoire de Dynamique Cellulaire, CNRS-UMR5539, Université de Montpellier II, 34095 Montpellier cedex 5,2 France

Received 25 June 2001/Returned for modification 18 July 2001/Accepted 13 August 2001

RhoG is a member of the Rho family of GTPases that activates Rac1 and Cdc42 through a microtubule-dependent pathway. To gain understanding of RhoG downstream signaling, we performed a yeast two-hybrid screen from which we identified kinectin, a 156-kDa protein that binds in vitro to conventional kinesin and enhances microtubule-dependent kinesin ATPase activity. We show that RhoGGTP specifically interacts with the central domain of kinectin, which also contains a RhoA binding domain in its C terminus. Interaction was confirmed by coprecipitation of kinectin with active RhoGG12V in COS-7 cells. RhoG, kinectin, and kinesin colocalize in REF-52 and COS-7 cells, mainly in the endoplasmic reticulum but also in lysosomes. Kinectin distribution in REF-52 cells is modulated according to endogenous RhoG activity. In addition, by using injection of anti-kinectin antibodies that challenge RhoG-kinectin interaction or by blocking anti-kinesin antibodies, we show that RhoG morphogenic activity relies on kinectin interaction and kinesin activity. Finally, kinectin overexpression elicits Rac1- and Cdc42-dependent cytoskeletal effects and switches cells to a RhoA phenotype when RhoG activity is inhibited or microtubules are disrupted. The functional links among RhoG, kinectin, and kinesin are further supported by time-lapse videomicroscopy of COS-7 cells, which showed that the microtubule-dependent lysosomal transport is facilitated by RhoG activation or kinectin overexpression and is severely stemmed upon RhoG inhibition. These data establish that kinectin is a key mediator of microtubule-dependent RhoG activity and suggest that kinectin also mediates RhoG- and RhoA-dependent antagonistic pathways.

* Corresponding author. Mailing address: Centre de Recherche en Biochimie Macromoléculaire, CNRS-UPR1086, 1919 Route de Mende 34293, Montpellier cedex 5, France. Phone: 33 467613356. Fax: 33 467521559. E-mail: fort{at}crbm.cnrs-mop.fr.

Molecular and Cellular Biology, December 2001, p. 8022-8034, Vol. 21, No. 23
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.23.8022-8034.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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