Molecular mechanisms underlying vesicle transport

Vesicles mediate trafficking pathways throughout the cell. This requires the process of vesicle transport to be highly specific. One of the major aims of cell biology is to understand how this specificity is achieved. Several classes of proteins regulate various stages of the transport process and contribute to the specificity of membrane transport. SNARE (soluble NSF attachment protein receptor) proteins belonging to the syntaxin, SNAP-25, and VAMP (vesicle-associated membrane protein) families form complexes with each other and play prominent roles during membrane fusion. In order to fully understand the organization of membrane transport routes in mammalian cells, it remains necessary to characterize the entire spectrum of SNARE proteins. To this end we characterized seven new mammalian proteins which we propose to be SNAREs important in intracellular membrane trafficking. In addition, we carried out a detailed investigation of the SNARE protein VAMP-7. VAMP-7 localizes predominantly to late endosomes and appears to function in a trafficking step between endosomes and lysosomes. It has been a matter of much debate as to how SNAREs contribute to membrane transport specificity. We have shown that SNARE-SNARE interactions themselves do not confer specificity to membrane trafficking. Another family of proteins that may impart specificity to vesicle transport is the Rab proteins. Rabs exert their function by interacting with distinct effector proteins. To gain additional insight into the role that Rab proteins play in regulating vesicle transport, we attempted to identify novel effector proteins for several rabs. In short, the study of SNARE proteins and Rab proteins is crucial for a better understanding of how membrane trafficking specificity is accomplished.