Cytosolic Ca2+ Modulates Golgi Structure Through PKCα-Mediated GRASP55 Phosphorylation
Stephen Ireland,
Saiprasad Ramnarayanan,
Mingzhou Fu,
Xiaoyan Zhang,
Jianchao Zhang,
Jie Li,
Dabel Emebo,
Yanzhuang Wang
Affiliations
Stephen Ireland
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Biological Sciences Building, 1105 North University Avenue, Ann Arbor, MI 48109-1085, USA
Saiprasad Ramnarayanan
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Biological Sciences Building, 1105 North University Avenue, Ann Arbor, MI 48109-1085, USA
Mingzhou Fu
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Biological Sciences Building, 1105 North University Avenue, Ann Arbor, MI 48109-1085, USA
Xiaoyan Zhang
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Biological Sciences Building, 1105 North University Avenue, Ann Arbor, MI 48109-1085, USA
Jianchao Zhang
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Biological Sciences Building, 1105 North University Avenue, Ann Arbor, MI 48109-1085, USA
Jie Li
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Biological Sciences Building, 1105 North University Avenue, Ann Arbor, MI 48109-1085, USA
Dabel Emebo
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Biological Sciences Building, 1105 North University Avenue, Ann Arbor, MI 48109-1085, USA
Yanzhuang Wang
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; Corresponding author
Summary: 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 Ca2+ and protein kinase Cα (PKCα) activity, which phosphorylates the Golgi stacking protein GRASP55. Significantly, activation of PKCα 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 Ca2+ modulates Golgi structure and function. : Biological Sciences; Cell Biology; Functional Aspects of Cell Biology Subject Areas: Biological Sciences, Cell Biology, Functional Aspects of Cell Biology
