title: The rab exchange factor Sec2p reversibly associates with the exocyst.
abstract: Activation of the rab GTPase, Sec4p, by its exchange factor, Sec2p, is needed for polarized transport of secretory vesicles to exocytic sites and for exocytosis. A small region in the C-terminal half of Sec2p regulates its localization. Loss of this region results in temperature-sensitive growth and the depolarized accumulation of secretory vesicles. Here, we show that Sec2p associates with the exocyst, an octameric effector of Sec4p involved in tethering secretory vesicles to the plasma membrane. Specifically, the exocyst subunit Sec15p directly interacts with Sec2p. This interaction normally occurs on secretory vesicles and serves to couple nucleotide exchange on Sec4p to the recruitment of the Sec4p effector. The mislocalization of Sec2p mutants correlates with dramatically enhanced binding to the exocyst complex. We propose that Sec2p is normally released from the exocyst after vesicle tethering so that it can recycle onto a new round of vesicles. The mislocalization of Sec2p mutants results from a failure to be released from Sec15p, blocking this recycling pathway.
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Martina
authors.initials: M
authors.lastname: Medkova
authors.forename: Y Ellen
authors.initials: YE
authors.lastname: France
authors.forename: Jeff
authors.initials: J
authors.lastname: Coleman
authors.forename: Peter
authors.initials: P
authors.lastname: Novick
mesh_terms: D001665:Binding Sites; D005089:Exocytosis / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors; D006868:Hydrolysis; D007700:Kinetics; D021122:Protein Subunits / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; C064456:SEC2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D005982:Glutathione Transferase; D019204:GTP-Binding Proteins