REGULATION OF RECEPTOR-MEDIATED ENDOCYTOSIS BY RHO AND RAC

PINOCYTOSIS and membrane ruffling are among the earliest and most dram atic cellular responses to stimulation by growth factors or other mito gens(1). The small Ras-related G proteins Rho and Rac have a regulator y role in membrane ruffling(1-3) and activated Rho has been shown to s timulate pinocytosis when microinjected into Xenopus oocytes(4). In co ntrast to these well established effects of Rho and Rac on plasma memb rane morphology and bulk pinocytosis, there has been no evidence for t heir involvement in the regulation of receptor-mediated endocytosis in clathrin-coated pits. Here we show that activated Rho and Rac inhibit transferrin-receptor-mediated endocytosis when expressed in intact ce lls. Furthermore, we have reconstituted these effects in a cell-free s ystem and established that Rho and Rac can regulate clathrin-coated ve sicle formation.