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Ypt/Rab GTPases and Traffic Coordination
Nava Segev 1
University of Illinois at Chicago 1
Abstract:
Transport of proteins and membranes between cellular compartments is mediated by vesicles
that bud from one compartment and fuse with the next. Ypt/Rab GTPases and their effectors
mediate all the known aspects of vesicular transport, from vesicle formation and motility, to
their targeting and fusion. An attractive idea is that Ypt/Rabs not only regulate individual
transport steps, but also integrate them into whole pathways and coordinate them with other
cellular processes. In yeast, three Ypts regulate the different steps of the exocytic pathway: Ypt1
is required for entry to the Golgi, the Ypt31/32 functional pair is necessary for exit from the
Golgi and Sec4 controls fusion of trans-Golgi vesicles with the plasma membrane. We have
uncovered three types of Ypt-mediated coordination mechanisms. First, we found that Ypt31/32
and Sec4 interact directly in a nucleotide-specific manner. This interaction is important for the
localization of Sec4 to trans-Golgi vesicles, thereby coupling Ypt31/32-mediated vesicle
formation and motility with Sec4-mediated tethering and fusion of these vesicles. Second, we
discovered that sequential activation of Ypt1 and Ypt31/32 by the modular complex TRAPP
coordinates Golgi entry and exit, thus integrating these two transport steps into a whole
pathway. Third, we identified novel effectors of Ypt1 and Ypt31/32 that serve to coordinate the
exocytic pathway with other cellular process like autophagy and ubiquitination. In summary, we
propose direct GTPase interactions, sequential activation and interaction with novel effectors as
mechanisms by which the highly conserved Ypt/Rab GTPases coordinate trafficking inside cells.