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A Rac switch regulates random versus directionally persistent cell migration

¹ Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892
² Division of Basic Science, Fox Chase Cancer Center, Philadelphia, PA 19111

Correspondence to Kenneth Yamada: kenneth.yamada{at}nih.gov

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.

R. Pankov's present address is Department of Cytology, Histology, and Embryology, Faculty of Biology, Sofia University, Sofia, 1421, Bulgaria.

M. Araki's present address is Moji Rosai Hospital, Moji-ku, Kitakyushu, Fukuoka, 801-8502, Japan.

K. Clark's present address is Department of Biochemistry, University of Leicester, University Road, Leicester LE1 7RH, UK.

Abbreviations used in this paper: 2D, two-dimensional; 3D, three-dimensional; PI3K, phosphatidylinositol 3'-kinase; si, small interfering.

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