VCIP135, a novel essential factor for p97/p47-mediated membrane fusion, is required for Golgi and ER assembly in vivo

doi:10.1083/jcb.200208112

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Published 9 December 2002. doi:10.1083/jcb.200208112

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© The Rockefeller University Press, 0021-9525/2002/12/855 $5.00
The Journal of Cell Biology, Volume 159, Number 5, 855-866

Article

VCIP135, a novel essential factor for p97/p47-mediated membrane fusion, is required for Golgi and ER assembly in vivo

Keiji Uchiyama¹, Eija Jokitalo², Fumi Kano³, Masayuki Murata³, Xiaodong Zhang⁴, Benito Canas⁵, Richard Newman⁶, Catherine Rabouille⁷, Darryl Pappin⁵, Paul Freemont⁴ and Hisao Kondo¹^,8

¹ Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY, United Kingdom
² Institute of Biotechnology, University of Helsinki, Helsinki FIN-00014, Finland
³ National Institute for Physiological Sciences, Okazaki 444-8585, Japan
⁴ Centre for Structural Biology, Imperial College of Science, Technology and Medicine, London SW7 2AZ, United Kingdom
⁵ Clinical Pharmacology, Imperial College School of Medicine, London W12 0NN, United Kingdom
⁶ European Molecular Biology Laboratory-European Bioinformatics Institute, Cambridge CB10 1SD, United Kingdom
⁷ University Medical Centre Utrecht, Academic Ziekhuis Utrecht, 3584CX Utrecht, Netherlands
⁸ PREST and SORST, Japan Science and Technology Corporation, Saitama 332-0012, Japan

Address correspondence to Hisao Kondo, Cambridge Institute for Medical Research, Rm 5.36, University of Cambridge, Wellcome Trust/MRC Bldg., Hills Rd., Cambridge CB2 2XY, UK. Tel.: 44-1223-762632. Fax: 44-1223-762640. E-mail: hk228{at}cam.ac.uk

NSF and p97 are ATPases required for the heterotypic fusionof transport vesicles with their target membranes and the homotypicfusion of organelles. NSF uses ATP hydrolysis to dissociateNSF/SNAPs/SNAREs complexes, separating the v- and t-SNAREs,which are then primed for subsequent rounds of fusion. In contrast,p97 does not dissociate the p97/p47/SNARE complex even in thepresence of ATP. Now we have identified a novel essential factorfor p97/p47-mediated membrane fusion, named VCIP135 (valosin-containingprotein [VCP][p97]/p47 complex-interacting protein, p135), andshow that it binds to the p97/p47/syntaxin5 complex and dissociatesit via p97 catalyzed ATP hydrolysis. In living cells, VCIP135and p47 are shown to function in Golgi and ER assembly.

Key Words: membrane fusion; p97; VCIP135; Golgi; ER

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