J. Cell Biol., Volume 141, Number 1, April 6, 1998 187-197

A New Member of the Rho Family, Rnd1, Promotes Disassembly of Actin Filament Structures and Loss of Cell Adhesion

Catherine D. Nobes,^§ Inger Lauritzen,^* Marie-Geneviève Mattei, Sonia Paris,^* Alan Hall,^§ and Pierre Chardin^*

^* Institut de Pharmacologie, Centre National de la Recherche Scientifique UPR 411, 06560 Valbonne, France;  Institut National de la Sante et de la Recherche Medicale U.406, Faculté de Médecine de la Timone, 13385 Marseille Cedex, France; and ^§ Medical Research Council Laboratory for Molecular Cell Biology, Cancer Research Campaign Oncogene and Signal Transduction Group and Department of Biochemistry, University College London, London WC1E 7BT, United Kingdom

Members of the Rho GTPase family regulate the organization of the actin cytoskeleton in response to extracellular growth factors. We have identified three proteins that form a distinct branch of the Rho family: Rnd1, expressed mostly in brain and liver; Rnd2, highly expressed in testis; and Rnd3/RhoE, showing a ubiquitous low expression. At the subcellular level, Rnd1 is concentrated at adherens junctions both in confluent fibroblasts and in epithelial cells. Rnd1 has a low affinity for GDP and spontaneously exchanges nucleotide rapidly in a physiological buffer. Furthermore, Rnd1 lacks intrinsic GTPase activity suggesting that in vivo, it might be constitutively in a GTP-bound form. Expression of Rnd1 or Rnd3/RhoE in fibroblasts inhibits the formation of actin stress fibers, membrane ruffles, and integrin-based focal adhesions and induces loss of cell-substrate adhesion leading to cell rounding (hence Rnd for "round"). We suggest that these proteins control rearrangements of the actin cytoskeleton and changes in cell adhesion.

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