title: Ypt1/Rab1 regulates Hrr25/CK1δ kinase activity in ER-Golgi traffic and macroautophagy.
abstract: ER-derived COPII-coated vesicles are conventionally targeted to the Golgi. However, during cell stress these vesicles also become a membrane source for autophagosomes, distinct organelles that target cellular components for degradation. How the itinerary of COPII vesicles is coordinated on these pathways remains unknown. Phosphorylation of the COPII coat by casein kinase 1 (CK1), Hrr25, contributes to the directional delivery of ER-derived vesicles to the Golgi. CK1 family members are thought to be constitutively active kinases that are regulated through their subcellular localization. Instead, we show here that the Rab GTPase Ypt1/Rab1 binds and activates Hrr25/CK1δ to spatially regulate its kinase activity. Consistent with a role for COPII vesicles and Hrr25 in membrane traffic and autophagosome biogenesis, hrr25 mutants were defective in ER-Golgi traffic and macroautophagy. These studies are likely to serve as a paradigm for how CK1 kinases act in membrane traffic.
authors.affiliation: Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Saralin
authors.initials: S
authors.lastname: Davis
authors.affiliation: Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Shekar
authors.initials: S
authors.lastname: Menon
authors.affiliation: Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Jinzhong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Jingzhen
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Serena
authors.initials: S
authors.lastname: Cervantes
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Miller
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093 sfnovick@ucsd.edu.
authors.forename: Susan
authors.initials: S
authors.lastname: Ferro-Novick
mesh_terms: D001343:Autophagy; D022181:COP-Coated Vesicles / Q000378:metabolism; D047389:Casein Kinase I / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D006056:Golgi Apparatus / Q000201:enzymology*; D006801:Humans; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000502:physiology*; D020691:rab GTP-Binding Proteins / Q000502:physiology*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D047389:Casein Kinase I; C070775:HRR25 protein, S cerevisiae; C060755:YPT1 protein, S cerevisiae; D020691:rab GTP-Binding Proteins