VCIP135, a novel essential factor for p97/p47-mediated membrane fusion, is required for Golgi and ER assembly in vivo.
NSF and p97 are ATPases required for the heterotypic fusion of transport vesicles with their target membranes and the homotypic fusion of organelles. NSF uses ATP hydrolysis to dissociate NSF/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 the presence of ATP. Now we have identified a novel essential factor for p97/p47-mediated membrane fusion, named VCIP135 (valosin-containing protein [VCP][p97]/p47 complex-interacting protein, p135), and show that it binds to the p97/p47/syntaxin5 complex and dissociates it via p97 catalyzed ATP hydrolysis. In living cells, VCIP135 and p47 are shown to function in Golgi and ER assembly.
Uchiyama
Keiji
K
Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY, United Kingdom.
Jokitalo
Eija
E
Kano
Fumi
F
Murata
Masayuki
M
Zhang
Xiaodong
X
Canas
Benito
B
Newman
Richard
R
Rabouille
Catherine
C
Pappin
Darryl
D
Freemont
Paul
P
Kondo
Hisao
H
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D015415:Biomarkers / Q000032:analysis; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D017124:Conserved Sequence; D006224:Cricetinae; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism; D053487:DEAD-box RNA Helicases; D010450:Endopeptidases; D004721:Endoplasmic Reticulum / Q000502:physiology*; D006056:Golgi Apparatus / Q000502:physiology*; D006868:Hydrolysis; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000166:cytology; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D008954:Models, Biological; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology*; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D000074405:Valosin Containing Protein
D015415:Biomarkers; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D010455:Peptides; C046951:valosin; C075446:Ddx39b protein, rat; D010450:Endopeptidases; C470473:Vcpip1 protein, rat; D000251:Adenosine Triphosphatases; D053487:DEAD-box RNA Helicases; D000074405:Valosin Containing Protein; C000614180:Vcp protein, rat