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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.
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