A role for ADP ribosylation factor in the control of cargo uptake during COPI-coated vesicle biogenesis

ARF-mediated hydrolysis of GTP has been demonstrated to regulate coat disas sembly of Golgi-derived COPI transport vesicles (Tanigawa, G., Orci, L., Am herdt, M., Ravazzola, M., Helms, J.B. and Rothman, J.E. (1993) J. Cell Biol . 123, 1365-1371). In addition, a requirement for GTP hydrolysis at an earl y stage of COPI vesicle biogenesis has been established since cargo uptake is impaired in the presence of GTP gamma S (Nickel, W., Malsam, J., Gorgas, K., Ravazzola, M., Jenne, N., Helms, J.B. and Wieland, F.T. (1998) J. Cell Sci. 111, 3081-3090), a non-hydrolyzahle analogue of GTP. We now demonstra te that the GTPase involved in the regulation of cargo uptake is ARF, revea ling a multi-functional role of this GTPase in COPI-mediated vesicular tran sport. The molecular mechanism of cargo uptake as well as the functional im plications of these findings on the overall process of COPI vesicle biogene sis are discussed. (C) 1999 Federation of European Biochemical Societies.