Unfolded protein response regulates yeast small GTPase Arl1p activation at late Golgi via phosphorylation of Arf GEF Syt1p

• Published in: Proceedings of the National Academy of Sciences - PNAS 2016-03, Vol.113 (12), p.E1683-E1690
• Main Authors: Hsu, Jia-Wei, Tang, Pei-Hua, Wang, I-Hao, Liu, Chia-Lun, Chen, Wen-Hui, Tsai, Pei-Chin, Chen, Kuan-Yu, Chen, Kuan-Jung, Yu, Chia-Jung, Lee, Fang-Jen S.
• Format: Article
• Language: English
• Subjects: Basic-Leucine Zipper Transcription Factors - metabolism; Biological Sciences; Cells; Endoplasmic Reticulum Stress; Genes, Reporter; Golgi Apparatus - metabolism; Guanine Nucleotide Exchange Factors - metabolism; Membrane Glycoproteins - metabolism; Membranes; Monomeric GTP-Binding Proteins - metabolism; Phosphorylation; PNAS Plus; Protein Processing, Post-Translational; Protein Transport; Protein-Serine-Threonine Kinases - metabolism; Proteins; Recombinant Fusion Proteins - metabolism; Repressor Proteins - metabolism; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; Unfolded Protein Response - physiology; Vesicular Transport Proteins - metabolism; Yeast
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1518260113

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 in IRE1-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.