Rab GTPases networks in membrane traffic in Saccharomyces cerevisiae

Abstract

Intracellular membrane tra‹cking between membranous compartments is essential for organelle biogenesis, structure, and identity. Rab/Ypt GTPases are well-characterized regulators of intracellular membrane tra‹cking, functioning as molecular switches that alternate between GTP- and GDP-bound forms. In Saccharomyces cerevisiae, 11 Rab/ Ypt GTPases have been identiˆed and their functions are known to be conserved in their mammalian counterparts. In yeast, the secretory pathway is regulated by sequential activation and inactivation (the so-called Rab cascade) of three types of yeast Rab protein -Ypt1p, Ypt31p/32p and Sec4p -via speciˆc guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). In addition to these Rabs, we and others have recently demonstrated that Ypt6p is predominantly localized to the early Golgi compartment, and functions as another regulator of anterograde transport for intra-Golgi tra‹cking in the secretory pathway. On the other hand, the endocytic pathway is known to be regulated by three yeast Rab5s (Vps21p, Ypt52p and Ypt53p) and one Rab7 (Ypt7p). Rab5 and Rab7 are key determinants of endosome identity, and the Rab5-Rab7 cascade is important for the progression from early to late endosome. Our recent study demonstrates that the endocytic pathway branches into two vacuolar targeting pathways, the Rab5-dependent vacuole protein sorting (VPS) pathway and the Rab5-independent pathway. In this review, we focus on recent advances in our understanding of molecular mechanisms that regulate the localization and activity of yeast Rab GTPases in intracellular membrane trafficcking.