PMID- 32179476 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210110 IS - 2589-0042 (Electronic) IS - 2589-0042 (Print) IS - 2589-0042 (Linking) VI - 23 IP - 3 DP - 2020 Mar 27 TI - Cytosolic Ca(2+) Modulates Golgi Structure Through PKCalpha-Mediated GRASP55 Phosphorylation. PG - 100952 LID - S2589-0042(20)30136-X [pii] LID - 10.1016/j.isci.2020.100952 [doi] LID - 100952 AB - It has been well documented that the ER responds to cellular stresses through the unfolded protein response (UPR), but it is unknown how the Golgi responds to similar stresses. In this study, we treated HeLa cells with ER stress inducers, thapsigargin (TG), tunicamycin (Tm), and dithiothreitol (DTT), and found that only TG treatment resulted in Golgi fragmentation. TG induced Golgi fragmentation at a low dose and short time when UPR was undetectable, indicating that Golgi fragmentation occurs independently of ER stress. Further experiments demonstrated that TG induces Golgi fragmentation through elevating intracellular Ca(2+) and protein kinase Calpha (PKCalpha) activity, which phosphorylates the Golgi stacking protein GRASP55. Significantly, activation of PKCalpha with other activating or inflammatory agents, including phorbol 12-myristate 13-acetate and histamine, modulates Golgi structure in a similar fashion. Hence, our study revealed a novel mechanism through which increased cytosolic Ca(2+) modulates Golgi structure and function. CI - Copyright (c) 2020 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Ireland, Stephen AU - Ireland S AD - Department of Molecular, Cellular and Developmental Biology, University of Michigan, Biological Sciences Building, 1105 North University Avenue, Ann Arbor, MI 48109-1085, USA. FAU - Ramnarayanan, Saiprasad AU - Ramnarayanan S AD - Department of Molecular, Cellular and Developmental Biology, University of Michigan, Biological Sciences Building, 1105 North University Avenue, Ann Arbor, MI 48109-1085, USA. FAU - Fu, Mingzhou AU - Fu M AD - Department of Molecular, Cellular and Developmental Biology, University of Michigan, Biological Sciences Building, 1105 North University Avenue, Ann Arbor, MI 48109-1085, USA. FAU - Zhang, Xiaoyan AU - Zhang X AD - Department of Molecular, Cellular and Developmental Biology, University of Michigan, Biological Sciences Building, 1105 North University Avenue, Ann Arbor, MI 48109-1085, USA. FAU - Zhang, Jianchao AU - Zhang J AD - Department of Molecular, Cellular and Developmental Biology, University of Michigan, Biological Sciences Building, 1105 North University Avenue, Ann Arbor, MI 48109-1085, USA. FAU - Li, Jie AU - Li J AD - Department of Molecular, Cellular and Developmental Biology, University of Michigan, Biological Sciences Building, 1105 North University Avenue, Ann Arbor, MI 48109-1085, USA. FAU - Emebo, Dabel AU - Emebo D AD - Department of Molecular, Cellular and Developmental Biology, University of Michigan, Biological Sciences Building, 1105 North University Avenue, Ann Arbor, MI 48109-1085, USA. FAU - Wang, Yanzhuang AU - Wang Y AD - Department of Molecular, Cellular and Developmental Biology, University of Michigan, Biological Sciences Building, 1105 North University Avenue, Ann Arbor, MI 48109-1085, USA; Department of Neurology, University of Michigan School of Medicine, Ann Arbor, MI 48109-1085, USA. Electronic address: yzwang@umich.edu. LA - eng GR - R35 GM130331/GM/NIGMS NIH HHS/United States GR - R56 AG062225/AG/NIA NIH HHS/United States PT - Journal Article DEP - 20200228 PL - United States TA - iScience JT - iScience JID - 101724038 PMC - PMC7078314 OTO - NOTNLM OT - Biological Sciences OT - Cell Biology OT - Functional Aspects of Cell Biology COIS- Declaration of Interests The authors declare no competing financial interests. EDAT- 2020/03/18 06:00 MHDA- 2020/03/18 06:01 PMCR- 2020/02/28 CRDT- 2020/03/18 06:00 PHST- 2019/10/28 00:00 [received] PHST- 2020/01/31 00:00 [revised] PHST- 2020/02/25 00:00 [accepted] PHST- 2020/03/18 06:00 [pubmed] PHST- 2020/03/18 06:01 [medline] PHST- 2020/03/18 06:00 [entrez] PHST- 2020/02/28 00:00 [pmc-release] AID - S2589-0042(20)30136-X [pii] AID - 100952 [pii] AID - 10.1016/j.isci.2020.100952 [doi] PST - ppublish SO - iScience. 2020 Mar 27;23(3):100952. doi: 10.1016/j.isci.2020.100952. Epub 2020 Feb 28.