title: Sit4p/PP6 regulates ER-to-Golgi traffic by controlling the dephosphorylation of COPII coat subunits.
abstract: Traffic from the endoplasmic reticulum (ER) to the Golgi complex is initiated when the activated form of the GTPase Sar1p recruits the Sec23p-Sec24p complex to ER membranes. The Sec23p-Sec24p complex, which forms the inner shell of the COPII coat, sorts cargo into ER-derived vesicles. The coat inner shell recruits the Sec13p-Sec31p complex, leading to coat polymerization and vesicle budding. Recent studies revealed that the Sec23p subunit sequentially interacts with three different binding partners to direct a COPII vesicle to the Golgi. One of these binding partners is the serine/threonine kinase Hrr25p. Hrr25p phosphorylates the COPII coat, driving the membrane-bound pool into the cytosol. The phosphorylated coat cannot rebind to the ER to initiate a new round of vesicle budding unless it is dephosphorylated. Here we screen all known protein phosphatases in yeast to identify one whose loss of function alters the cellular distribution of COPII coat subunits. This screen identifies the PP2A-like phosphatase Sit4p as a regulator of COPII coat dephosphorylation. Hyperphosphorylated coat subunits accumulate in the sit4Δ mutant in vivo. In vitro, Sit4p dephosphorylates COPII coat subunits. Consistent with a role in coat recycling, Sit4p and its mammalian orthologue, PP6, regulate traffic from the ER to the Golgi complex.
authors.affiliation: Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Deepali
authors.initials: D
authors.lastname: Bhandari
authors.forename: Jinzhong
authors.initials: J
authors.lastname: Zhang
authors.forename: Shekar
authors.initials: S
authors.lastname: Menon
authors.forename: Christopher
authors.initials: C
authors.lastname: Lord
authors.forename: Shuliang
authors.initials: S
authors.lastname: Chen
authors.forename: Jared R
authors.initials: JR
authors.lastname: Helm
authors.forename: Kevin
authors.initials: K
authors.lastname: Thorsen
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Corbett
authors.forename: Jesse C
authors.initials: JC
authors.lastname: Hay
authors.forename: Susan
authors.initials: S
authors.lastname: Ferro-Novick
mesh_terms: D000818:Animals; D022181:COP-Coated Vesicles / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; D054648:Protein Phosphatase 2; C104343:SIT4 protein, S cerevisiae