title: Phosphorylation regulates VCIP135 function in Golgi membrane fusion during the cell cycle.
abstract: The Golgi apparatus in mammalian cells consists of stacks that are often laterally linked into a ribbon-like structure. During cell division, the Golgi disassembles into tubulovesicular structures in the early stages of mitosis and reforms in the two daughter cells by the end of mitosis. Valosin-containing protein p97-p47 complex-interacting protein, p135 (VCIP135), an essential factor involved in p97-mediated membrane fusion pathways, is required for postmitotic Golgi cisternae regrowth and Golgi structure maintenance in interphase. However, how VCIP135 function is regulated in the cell cycle remains unclear. Here, we report that VCIP135 depletion by RNA interference results in Golgi fragmentation. VCIP135 function requires membrane association and p97 interaction, both of which are inhibited in mitosis by VCIP135 phosphorylation. We found that wild-type VCIP135, but not its phosphomimetic mutants, rescues Golgi structure in VCIP135-depleted cells. Our results demonstrate that VCIP135 phosphorylation regulates its Golgi membrane association and p97 interaction, and thus contributes to the tight control of the Golgi disassembly and reassembly process during the cell cycle.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, 830 North University Avenue, Ann Arbor, MI 48109-1048, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.forename: Honghao
authors.initials: H
authors.lastname: Zhang
authors.forename: Yanzhuang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D002453:Cell Cycle / Q000235:genetics*; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D005816:Genetic Complementation Test; D006056:Golgi Apparatus / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008561:Membrane Fusion / Q000235:genetics*; D009154:Mutation; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D028961:beta Karyopherins / Q000235:genetics* / Q000378:metabolism
chemical_list: C424166:KPNB1 protein, human; D034741:RNA, Small Interfering; D028961:beta Karyopherins; D010450:Endopeptidases; C581414:VCPIP1 protein, human
keywords: Cell cycle; Golgi fragmentation; Membrane association; Phosphorylation; VCIP135; p97