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Towards Investigating the Role of Rho GTPases in Cellular Perception of Gravity.  M. Aumailley1,2, Z. Zhang1, G. Chometon1, B. Eckes3, T. Krieg3 1Center for Biochemistry, 2Center for Molecular Medicine and 3Department of Dermatology, University of Cologne, Cologne, Germany.

   Small GTP-binding proteins of the Rho family (RhoA, Cdc42, Rac1) regulate the organisation and the turnover of the cell's cytoskeleton and adhesion structures. An important function of these cellular structures is to translate and counter-balance forces applied to, or generated by cells in order to maintain homeostasis and control cell movement. It is therefore logical to assume that Rho-GTPases are directly involved in cellular perception of gravity. To define an adequate cellular model allowing to investigate this issue, Lambert et al. (see abstract) have established stable cell lines expressing different mutants of the Rho proteins and we have performed functional analyses of mutant cells expressing constitutively active forms of either RhoA, Cdc42 or Rac1.

   At the light microscope level, the three cell lines differ by morphology, in particular by their ability to form cell-cell contacts, lamellipodia, membrane ruffles and filopodias. Constitutively active Cdc42 leads to premature and sustained adhesion of the cells to extracellular matrix proteins (collagens, laminins, fibronectin). Constitutively active Rac1 and Cdc42 induce active migration of the cells as observed by time-lapse video-microscopy, while constitutively active RhoA dramatically restricts cell movement. Finally the ability of cells to contract collagen lattices is reduced by constitutively active RhoA. In conclusion, our series of mutant cells appear well-suited to gain further knowledge on the molecular mechanisms of cellular perception of gravity.

(Supported by DLR 50WB0321)