![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 10, Issue 10, 3239-3250, October 1999
and
*Laboratory for Physiological Chemistry, Utrecht University, 3584 CG Utrecht, The Netherlands; and Rab5 is a regulatory GTPase of vesicle docking and fusion that is
involved in receptor-mediated endocytosis and pinocytosis. Introduction
of active Rab5 in cells stimulates the rate of endocytosis and vesicle
fusion, resulting in the formation of large endocytic vesicles, whereas
dominant negative Rab5 inhibits vesicle fusion. Here we show that
introduction of active Rab5 in fibroblasts also induced reorganization
of the actin cytoskeleton but not of microtubule filaments, resulting
in prominent lamellipodia formation. The Rab5-induced lamellipodia
formation did not require activation of PI3-K or the GTPases Ras, Rac,
Cdc42, or Rho, which are all strongly implicated in cytoskeletal
reorganization. Furthermore, lamellipodia formation by insulin, Ras, or
Rac was not affected by expression of dominant negative Rab5. In
addition, cells expressing active Rab5 displayed a dramatic stimulation
of cell migration, with the lamellipodia serving as the leading edge.
Both lamellipodia formation and cell migration were dependent on actin
polymerization but not on microtubules. These results demonstrate that
Rab5 induces lamellipodia formation and cell migration and that the
Rab5-induced lamellipodia formation occurs by a novel mechanism
independent of, and distinct from, PI3-K, Ras, or Rho-family GTPases.
Thus, Rab5 can control not only endocytosis but also actin cytoskeleton reorganization and cell migration, which provides strong support for an
intricate relationship between these processes.
Department of Pathology,
Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam,
The Netherlands
Corresponding author. E-mail address:
marcel.spaargaren{at}amc.uva.nl.
This article has been cited by other articles:
|
|
 |
|
  S.-C. Yip, M. El-Sibai, S. J. Coniglio, G. Mouneimne, R. J. Eddy, B. E. Drees, P. O. Neilsen, S. Goswami, M. Symons, J. S. Condeelis, et al. The distinct roles of Ras and Rac in PI 3-kinase-dependent protrusion during EGF-stimulated cell migration J. Cell Sci., September 1, 2007; 120(17): 3138 - 3146. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Vukmirica, P. Monzo, Y. Le Marchand-Brustel, and M. Cormont The Rab4A Effector Protein Rabip4 Is Involved in Migration of NIH 3T3 Fibroblasts J. Biol. Chem., November 24, 2006; 281(47): 36360 - 36368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Shulman, R. Pasvolsky, E. Woolf, V. Grabovsky, S. W. Feigelson, N. Erez, Y. Fukui, and R. Alon DOCK2 regulates chemokine-triggered lateral lymphocyte motility but not transendothelial migration Blood, October 1, 2006; 108(7): 2150 - 2158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Pellinen and J. Ivaska Integrin traffic. J. Cell Sci., September 15, 2006; 119(Pt 18): 3723 - 3731. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. L. Prigozhina and C. M. Waterman-Storer Decreased polarity and increased random motility in PtK1 epithelial cells correlate with inhibition of endosomal recycling. J. Cell Sci., September 1, 2006; 119(Pt 17): 3571 - 3582. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-W. Shin, M. Hayashi, S. Christoforidis, S. Lacas-Gervais, S. Hoepfner, M. R. Wenk, J. Modregger, S. Uttenweiler-Joseph, M. Wilm, A. Nystuen, et al. An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the endocytic pathway J. Cell Biol., August 15, 2005; 170(4): 607 - 618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. H. Le, P. van der Bent, G. Huls, M. van de Wetering, M. Loghman-Adham, A. C. M. Ong, J. P. Calvet, H. Clevers, M. H. Breuning, H. van Dam, et al. Aberrant Polycystin-1 Expression Results in Modification of Activator Protein-1 Activity, whereas Wnt Signaling Remains Unaffected J. Biol. Chem., June 25, 2004; 279(26): 27472 - 27481. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Topp, N. W. Gray, R. D. Gerard, and B. F. Horazdovsky Alsin Is a Rab5 and Rac1 Guanine Nucleotide Exchange Factor J. Biol. Chem., June 4, 2004; 279(23): 24612 - 24623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Sabo, A. F. Ikin, J. D. Buxbaum, and P. Greengard The Amyloid Precursor Protein and Its Regulatory Protein, FE65, in Growth Cones and Synapses In Vitro and In Vivo J. Neurosci., July 2, 2003; 23(13): 5407 - 5415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Tisdale Glyceraldehyde-3-phosphate Dehydrogenase Is Phosphorylated by Protein Kinase Ciota /lambda and Plays a Role in Microtubule Dynamics in the Early Secretory Pathway J. Biol. Chem., January 25, 2002; 277(5): 3334 - 3341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. D. Brown, A. L. Rozelle, H. L. Yin, T. Balla, and J. G. Donaldson Phosphatidylinositol 4,5-bisphosphate and Arf6-regulated membrane traffic J. Cell Biol., September 3, 2001; 154(5): 1007 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Symons and Y. Takai Ras GTPases: Singing in Tune Sci. Signal., February 6, 2001; 2001 (68): pe1 - pe1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Ridley Rho GTPases and cell migration J. Cell Sci., January 8, 2001; 114(15): 2713 - 2722. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. D. de Ruiter, R. M. F. Wolthuis, H. van Dam, B. M. T. Burgering, and J. L. Bos Ras-Dependent Regulation of c-Jun Phosphorylation Is Mediated by the Ral Guanine Nucleotide Exchange Factor-Ral Pathway Mol. Cell. Biol., November 15, 2000; 20(22): 8480 - 8488. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. L. Roberts, M. A. Barbieri, J. Ullrich, and P. D. Stahl Dynamics of rab5 activation in endocytosis and phagocytosis J. Leukoc. Biol., November 1, 2000; 68(5): 627 - 632. [Abstract] [Full Text]
|
|
