ASTROCYTE SPREADING IN RESPONSE TO THROMBIN AND LYSOPHOSPHATIDIC ACIDIS DEPENDENT ON THE RHO-GTPASE

Astrocytes are typically star shaped cells playing diverse roles in th e function of the nervous system. In astrocyte cultures established fr om the cerebral hemispheres of newborn rats, the cells have generally a polygonal fibroblast-like morphology, but acquire a stellate shape u pon serum removal. When the serine protease thrombin or the bioactive lipid lysophosphatidic acid is added, the stellate cells revert to the flat morphology. Here we show that the effect of these agents is medi ated via activation of the small GTP-binding protein Rho. Neither thro mbin nor lysophosphatidic acid induced spreading of astrocytes microin jected with C3 transferase, an exoenzyme which ADP-ribosylates and the reby inactivates Rho. In contrast, the response of cells injected with a dominant negative form of Rac was unaffected. In addition, the inje ction of active Rho into stellate astrocytes mimicked the effect of th rombin and lysophosphatidic acid and an injection of C3 into flat cell s grown in serum induced stellation. The conversion from a stellate to a spread morphology upon activation of Rho resulted in the formation of stress fibers and focal adhesions which most probably are key event s in establishing and stabilizing the altered cytoarchitecture. These results suggest that Rho plays a crucial role in determining the shape of astrocytes and thereby may modulate their interaction with neurons in vivo. (C) 1997 Wiley-Liss, Inc.