title: Unfolded protein response regulates yeast small GTPase Arl1p activation at late Golgi via phosphorylation of Arf GEF Syt1p.
abstract: ADP ribosylation factor (Arf) GTPases are key regulators of membrane traffic at the Golgi complex. In yeast, Arf guanine nucleotide-exchange factor (GEF) Syt1p activates Arf-like protein Arl1p, which was accompanied by accumulation of golgin Imh1p at late Golgi, but whether and how this function of Syt1p is regulated remains unclear. Here, we report that the inositol-requiring kinase 1 (Ire1p)-mediated unfolded protein response (UPR) modulated Arl1p activation at late Golgi. Arl1p activation was dependent on both kinase and endo-RNase activities of Ire1p. Moreover, constitutively active transcription factor Hac1p restored the Golgi localization of Arl1p and Imh1p inIRE1-deleted cells. Elucidating the mechanism of Ire1p-Hac1p axis actions, we found that it regulated phosphorylation of Syt1p, which enhances Arl1p activation, recruitment of Imh1p to the Golgi, and Syt1p interaction with Arl1p. Consistent with these findings, the induction of UPR by tunicamycin treatment increases phosphorylation of Syt1p, resulting in Arl1p activation. Thus, these findings clarify how the UPR influences the roles of Syt1p, Arl1p, and Imh1p in Golgi transport.
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei 100, Taiwan;
authors.forename: Jia-Wei
authors.initials: JW
authors.lastname: Hsu
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei 100, Taiwan;
authors.forename: Pei-Hua
authors.initials: PH
authors.lastname: Tang
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei 100, Taiwan;
authors.forename: I-Hao
authors.initials: IH
authors.lastname: Wang
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei 100, Taiwan;
authors.forename: Chia-Lun
authors.initials: CL
authors.lastname: Liu
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei 100, Taiwan;
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Chen
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei 100, Taiwan;
authors.forename: Pei-Chin
authors.initials: PC
authors.lastname: Tsai
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei 100, Taiwan;
authors.forename: Kuan-Yu
authors.initials: KY
authors.lastname: Chen
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei 100, Taiwan;
authors.forename: Kuan-Jung
authors.initials: KJ
authors.lastname: Chen
authors.affiliation: Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan.
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Yu
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei 100, Taiwan; fangjen@ntu.edu.tw.
authors.forename: Fang-Jen S
authors.identifier: http://orcid.org/0000-0002-2167-2426
authors.initials: FJ
authors.lastname: Lee
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D017930:Genes, Reporter; D006056:Golgi Apparatus / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D056811:Unfolded Protein Response / Q000502:physiology*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D020662:Guanine Nucleotide Exchange Factors; C091341:HAC1 protein, S cerevisiae; C117417:IMH1 protein, S cerevisiae; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C121631:SYT1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; C082863:IRE1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C487039:ARL1 protein, S cerevisiae; D020559:Monomeric GTP-Binding Proteins
keywords: ADP ribosylation factor; ER stress; GTPase; Golgi complex; UPR