Taking the Rabs off endocytosis The Rab family of small CTP-binding proteins have been implicated in the regulation of membrane traffic. Recent results suggest that Rab? and Rab5 govern rate-limiting steps in the endocytic pathway.

Transport between compartments of the exocytic and en- docytic pathways that is mediated by vesicular carriers, as first proposed by Palade [l], requires the regulation of both vesicle formation and the specificity of subsequent vesicle targetting. This dual regulation maintains the struc- tural and biochemical integrity of each compartment and imparts directionality on the transport process. To date, the molecular mechanisms that ensure transport vesicles dock and fuse with their correct targets have remained ob- scure. The Ras-related Rab family of low molecular weight (21-26kD) GTP-binding proteins appear to have at least some of the credentials for such a role. The Rab proteins - so-called because the first members were identified as Ras-like proteins in a rat brain cDNA library - are the mammalian counterparts of two small GTP-binding proteins, Yptl and Sec4, of Saccharomyces cerevkiae. Work on these yeast proteins provided the first insight into the function of Rabs, when mutations of the WTl and SEC4 genes were found to cause defects in the exocytic pathway. SEC4 mutations are associated with the accumulation of stage-specific vesicular intermediates