title: Sequential interactions with Sec23 control the direction of vesicle traffic.
abstract: How the directionality of vesicle traffic is achieved remains an important unanswered question in cell biology. The Sec23p/Sec24p coat complex sorts the fusion machinery (SNAREs) into vesicles as they bud from the endoplasmic reticulum (ER). Vesicle tethering to the Golgi begins when the tethering factor TRAPPI binds to Sec23p. Where the coat is released and how this event relates to membrane fusion is unknown. Here we use a yeast transport assay to demonstrate that an ER-derived vesicle retains its coat until it reaches the Golgi. A Golgi-associated kinase, Hrr25p (CK1δ orthologue), then phosphorylates the Sec23p/Sec24p complex. Coat phosphorylation and dephosphorylation are needed for vesicle fusion and budding, respectively. Additionally, we show that Sec23p interacts in a sequential manner with different binding partners, including TRAPPI and Hrr25p, to ensure the directionality of ER-Golgi traffic and prevent the back-fusion of a COPII vesicle with the ER. These events are conserved in mammalian cells.
authors.affiliation: Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California at San Diego, La Jolla, California 92093-0668, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Lord
authors.forename: Deepali
authors.initials: D
authors.lastname: Bhandari
authors.forename: Shekar
authors.initials: S
authors.lastname: Menon
authors.forename: Majid
authors.initials: M
authors.lastname: Ghassemian
authors.forename: Deborah
authors.initials: D
authors.lastname: Nycz
authors.forename: Jesse
authors.initials: J
authors.lastname: Hay
authors.forename: Pradipta
authors.initials: P
authors.lastname: Ghosh
authors.forename: Susan
authors.initials: S
authors.lastname: Ferro-Novick
mesh_terms: D000818:Animals; D022181:COP-Coated Vesicles / Q000378:metabolism; D047389:Casein Kinase I / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D051381:Rats; D050600:SNARE Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D050600:SNARE Proteins; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; C406327:transport protein particle, TRAPP; D047389:Casein Kinase I; C070775:HRR25 protein, S cerevisiae