|
|
|
|
A more recent version of this article appeared on December 1, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on April 24, 2003
Revised on August 1, 2003
Accepted on August 20, 2003
1 Centre de Recherches en Biochimie Macromoléculaire, CNRS UPR 1086
2 Institut Curie, CNRS UMR 144, 26, rue d'Ulm, 75248 Paris Cedex 05, France
3 Institut de Génétique moléculaire, CNRS UMR 5124, 1919 route de Mende, 34293 Montpellier Cedex 05, France
4 Centre de Recherches en Biochimie Macromoléculaire, CNRS UPR 1086
* Corresponding author. E-mail address: blangy{at}crbm.cnrs-mop.fr.
Rho GTPases are key regulators of actin dynamics. We report that the Rho GTPase TCL, which is closely related to Cdc42 and TC10, localizes to the plasma membrane in HeLa cells, suggesting a role in the early endocytic pathway. Receptor dependent internalization of transferrin (Tf) is unaffected by suppression of endogenous TCL by siRNA treatment. However, Tf accumulates in Rab5-positive uncoated endocytic vesicles and fails to reach the EEA1-positive early endosomal compartments and the pericentriolar recycling endosomes. Moreover, Tf release upon TCL knockdown is significantly slower. Conversely, in the presence of dominant active TCL, internalized Tf accumulates in EEA1-positive early/sorting endosomes and not in perinuclear recycling endosomes. Tf recycles directly from the early/sorting endosomes and it is normally released by the cells. The same phenotype is generated by replacing the C terminus of dominant active Cdc42 and TC10 with that of TCL, indicating that all three proteins share downstream effector proteins. Thus, TCL is essential for clathrin dependent endocytosed receptors to enter the early/sorting endosomes. Furthermore, the active GTPase favors direct recycling from early/sorting endosomes without accumulating in the perinuclear recycling endosomes.
This article has been cited by other articles:
![]() |
I. J. Lodhi, D. Bridges, S.-H. Chiang, Y. Zhang, A. Cheng, L. M. Geletka, L. S. Weisman, and A. R. Saltiel Insulin Stimulates Phosphatidylinositol 3-Phosphate Production via the Activation of Rab5 Mol. Biol. Cell, July 1, 2008; 19(7): 2718 - 2728. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Ieguchi, S. Ueda, T. Kataoka, and T. Satoh Role of the Guanine Nucleotide Exchange Factor Ost in Negative Regulation of Receptor Endocytosis by the Small GTPase Rac1 J. Biol. Chem., August 10, 2007; 282(32): 23296 - 23305. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Harsay and R. Schekman Avl9p, a Member of a Novel Protein Superfamily, Functions in the Late Secretory Pathway Mol. Biol. Cell, April 1, 2007; 18(4): 1203 - 1219. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Boureux, E. Vignal, S. Faure, and P. Fort Evolution of the Rho Family of Ras-Like GTPases in Eukaryotes Mol. Biol. Evol., January 1, 2007; 24(1): 203 - 216. [Abstract] [Full Text] [PDF] |
||||