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.
Citation
Raman, M., Sergeev, M., Garnaas, M., Lydeard, J.R., Huttlin, E.L., Goessling, W., Shah, J.V., Harper, J.W. (2015) Systematic proteomics of the VCP-UBXD adaptor network identifies a role for UBXN10 in regulating ciliogenesis. Nature cell biology. 17(10):1356-69.
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 .
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping