title: Interactions between Rabs, tethers, SNAREs and their regulators in exocytosis.
abstract: Sec2p is the exchange factor that activates Sec4p, the Rab GTPase controlling the final stage of the yeast exocytic pathway. Sec2p is recruited to secretory vesicles by Ypt32-GTP, a Rab controlling exit from the Golgi. Sec15p, a subunit of the octameric exocyst tethering complex and an effector of Sec4p, binds to Sec2p on secretory vesicles, displacing Ypt32p. Sec2p mutants defective in the region 450-508 amino acids bind to Sec15p more tightly. In these mutants, Sec2p accumulates in the cytosol in a complex with the exocyst and is not recruited to vesicles by Ypt32p. Thus the region 450-508 amino acids negatively regulates the association of Sec2p with the exocyst, allowing it to recycle on to new vesicles. The structures of one nearly full-length exocyst subunit and three partial subunits have been determined and, despite very low sequence identity, all form rod-like structures built of helical bundles stacked end to end. These rods may bind to each other along their sides to form the assembled complex. While Sec15p binds Sec4-GTP on the vesicle, other subunits bind Rho GTPases on the plasma membrane, thus tethering vesicles to exocytic sites. Sec4-GTP also binds Sro7p, a yeast homologue of the Drosophila lgl (lethal giant larvae) tumour suppressor. Sro7 also binds to Sec9p, a SNAP25 (25 kDa synaptosome-associated protein)-like t-SNARE [target-membrane-associated SNARE (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor)], and can form a Sec4p-Sro7p-Sec9p ternary complex. Overexpression of Sec4p, Sro7p or Sec1p (another SNARE regulator) can bypass deletions of three different exocyst subunits. Thus promoting SNARE function can compensate for tethering defects.
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA. peter.novick@yale.edu
authors.forename: P
authors.initials: P
authors.lastname: Novick
authors.forename: M
authors.initials: M
authors.lastname: Medkova
authors.forename: G
authors.initials: G
authors.lastname: Dong
authors.forename: A
authors.initials: A
authors.lastname: Hutagalung
authors.forename: K
authors.initials: K
authors.lastname: Reinisch
authors.forename: B
authors.initials: B
authors.lastname: Grosshans
mesh_terms: D002462:Cell Membrane / Q000502:physiology; D005089:Exocytosis / Q000502:physiology*; D006706:Homeostasis; D008954:Models, Biological; D050600:SNARE Proteins / Q000378:metabolism*; D022142:Secretory Vesicles / Q000502:physiology*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D050600:SNARE Proteins; D020691:rab GTP-Binding Proteins