title: VCIP135 deubiquitinase and its binding protein, WAC, in p97ATPase-mediated membrane fusion.
abstract: Two distinct p97 membrane fusion pathways are required for Golgi biogenesis: the p97/p47 and p97/p37 pathways. VCIP135 is necessary for both pathways, while its deubiquitinating activity is required only for the p97/p47 pathway. We have now identified a novel VCIP135-binding protein, WAC. WAC localizes to the Golgi as well as the nucleus. In Golgi membranes, WAC is involved in a complex containing VCIP135 and p97. WAC directly binds to VCIP135 and increases its deubiquitinating activity. siRNA experiments revealed that WAC is required for Golgi biogenesis. In an in vitro Golgi reformation assay, WAC was necessary only for p97/p47-mediated Golgi reassembly, but not for p97/p37-mediated reassembly. WAC is hence thought to function in p97/p47-mediated Golgi membrane fusion by activating the deubiquitinating function of VCIP135. We also showed that the two p97 pathways function in ER membrane fusion as well. An in vitro ER reformation assay revealed that both pathways required VCIP135 but not its deubiquitinating activity for their ER membrane fusion. This was consistent with the finding that WAC is unnecessary for p97-mediated ER membrane fusion.
authors.affiliation: Department of Molecular Cell Biology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Totsukawa
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Keiji
authors.initials: K
authors.lastname: Uchiyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Toh
authors.forename: Kaori
authors.initials: K
authors.lastname: Tamura
authors.forename: Hisao
authors.initials: H
authors.lastname: Kondo
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D010450:Endopeptidases; C470473:Vcpip1 protein, rat; D000251:Adenosine Triphosphatases; C404942:p97 ATPase