Eukaryotic cells use vesicular transport to effect processes as diverse as synaptic transmission and the polarized growth of the yeast Saccharomyces cerevisiae. The secretory pathway consists of a series of discreet stages in which proteins in one organelle are selectively packaged into small vesicles that are in turn transported through the cytoplasm and ultimately fuse with the next organelle along the pathway. Each step of membrane trafficking; budding, translocation, targeting and fusion of vesicles, is facilitated by a diverse array of proteins. Sec2p – a guanine nucleotide exchange factor for the small GTPase Sec4p - is one of the essential factors regulating Golgi to plasma membrane transport in yeast. Activation of Sec4p by Sec2p is involved in polarized transport of vesicles to the sites of secretion. Temperature sensitive mutations in sec2 and sec4 result in the depolarized accumulation of secretory vesicles and exhibit a tight block in secretion. While the temperature sensitive mutation sec2-78 does not affect its nucleotide exchange activity, the protein is mislocalized. The proper localization of Sec2p to secretory vesicles is essential for its function and is largely independent of Sec4p. A member of the Rab GTPase family, Ypt32p, regulates Sec2p function by recruiting it to vesicles. However, Ypt32p alone cannot account for the tight regulation of Sec2p localization and therefore other factor(s) must be involved in this process. The major goal of this research proposal will be to establish the identity of this factor. Two possibilities will be explored, that this component is either of protein or lipid origin. In addition, I am interested in the possible functional link between Sec2p and the Exocyst, a large protein complex involved in tethering of vesicles to the plasma membrane. These studies will deepen our understanding of how Sec2p function is regulated and how it is connected to other processes involved in the polarized vesicle transport in yeast.

Last Updated 04-Apr-2002 Created by Ralph France france@astro.uconn.edu

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