1. A Rac switch regulates random versus directionally persistent cell migration.
- Author
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Pankov R, Endo Y, Even-Ram S, Araki M, Clark K, Cukierman E, Matsumoto K, and Yamada KM
- Subjects
- Cell Culture Techniques, Cell Surface Extensions metabolism, Cells, Cultured, Epithelial Cells cytology, Epithelial Cells metabolism, Fibroblasts cytology, Fibroblasts metabolism, Fibronectins metabolism, Guanosine Triphosphate metabolism, Humans, Integrins genetics, Integrins metabolism, Phosphatidylinositol 3-Kinases metabolism, Phosphoinositide-3 Kinase Inhibitors, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, Random Allocation, Signal Transduction physiology, cdc42 GTP-Binding Protein genetics, cdc42 GTP-Binding Protein metabolism, rac GTP-Binding Proteins genetics, rho GTP-Binding Proteins genetics, rho GTP-Binding Proteins metabolism, Cell Movement physiology, rac GTP-Binding Proteins metabolism
- Abstract
Directional migration moves cells rapidly between points, whereas random migration allows cells to explore their local environments. We describe a Rac1 mechanism for determining whether cell patterns of migration are intrinsically random or directionally persistent. Rac activity promoted the formation of peripheral lamellae that mediated random migration. Decreasing Rac activity suppressed peripheral lamellae and switched the cell migration patterns of fibroblasts and epithelial cells from random to directionally persistent. In three-dimensional rather than traditional two-dimensional cell culture, cells had a lower level of Rac activity that was associated with rapid, directional migration. In contrast to the directed migration of chemotaxis, this intrinsic directional persistence of migration was not mediated by phosphatidylinositol 3'-kinase lipid signaling. Total Rac1 activity can therefore provide a regulatory switch between patterns of cell migration by a mechanism distinct from chemotaxis.
- Published
- 2005
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