PUBLICATION

Systematic proteomics of the VCP-UBXD adaptor network identifies a role for UBXN10 in regulating ciliogenesis

Authors
Raman, M., Sergeev, M., Garnaas, M., Lydeard, J.R., Huttlin, E.L., Goessling, W., Shah, J.V., Harper, J.W.
ID
ZDB-PUB-150923-1
Date
2015
Source
Nature cell biology   17(10): 1356-69 (Journal)
Registered Authors
Garnaas, Maija, Goessling, Wolfram
Keywords
Ciliogenesis, Ubiquitylation
MeSH Terms
  • Adaptor Proteins, Signal Transducing/genetics
  • Adaptor Proteins, Signal Transducing/metabolism*
  • Adenosine Triphosphatases/genetics
  • Adenosine Triphosphatases/metabolism*
  • Animals
  • Cell Cycle Proteins/genetics
  • Cell Cycle Proteins/metabolism*
  • Cilia/metabolism*
  • Cilia/physiology
  • Cytoskeletal Proteins/genetics
  • Cytoskeletal Proteins/metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Immunoblotting
  • LLC-PK1 Cells
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Morphogenesis/physiology
  • Protein Binding
  • Protein Interaction Mapping/methods
  • Protein Interaction Maps*
  • Proteomics/methods*
  • RNA Interference
  • Swine
  • Tumor Suppressor Proteins/genetics
  • Tumor Suppressor Proteins/metabolism
PubMed
26389662 Full text @ Nat. Cell Biol.
Abstract
The AAA-ATPase VCP (also known as p97 or CDC48) uses ATP hydrolysis to 'segregate' ubiquitylated proteins from their binding partners. VCP acts through UBX-domain-containing adaptors that provide target specificity, but the targets and functions of UBXD proteins remain poorly understood. Through systematic proteomic analysis of UBXD proteins in human cells, we reveal a network of over 195 interacting proteins, implicating VCP in diverse cellular pathways. We have explored one such complex between an unstudied adaptor UBXN10 and the intraflagellar transport B (IFT-B) complex, which regulates anterograde transport into cilia. UBXN10 localizes to cilia in a VCP-dependent manner and both VCP and UBXN10 are required for ciliogenesis. Pharmacological inhibition of VCP destabilized the IFT-B complex and increased trafficking rates. Depletion of UBXN10 in zebrafish embryos causes defects in left-right asymmetry, which depends on functional cilia. This study provides a resource for exploring the landscape of UBXD proteins in biology and identifies an unexpected requirement for VCP-UBXN10 in ciliogenesis.
Errata / Notes
This article is corrected by ZDB-PUB-220906-36 .
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