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Kinectin is a key effector of RhoG microtubule-dependent cellular activity.

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 RhoG(GTP) 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 RhoG(G12V) 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.

Pubmed ID: 11689693


  • Vignal E
  • Blangy A
  • Martin M
  • Gauthier-Rouvière C
  • Fort P


Molecular and cellular biology

Publication Data

December 5, 2001

Associated Grants


Mesh Terms

  • Animals
  • Antibodies, Blocking
  • Biological Transport
  • Blood Proteins
  • COS Cells
  • Cytoskeleton
  • Endoplasmic Reticulum
  • Fibroblasts
  • GTP Phosphohydrolases
  • Gene Expression
  • Humans
  • Jurkat Cells
  • Kinesin
  • Lysosomes
  • Membrane Proteins
  • Microscopy, Video
  • Microtubules
  • Phenotype
  • Protein Binding
  • Protein Structure, Tertiary
  • Rats
  • Transfection
  • Two-Hybrid System Techniques
  • cdc42 GTP-Binding Protein
  • rac1 GTP-Binding Protein
  • rho GTP-Binding Proteins
  • rhoA GTP-Binding Protein