Raman M, Sergeev M, Garnaas M, Lydeard JR, Huttlin EL, Goessling W, Shah JV, Harper JW. Systematic proteomics of the VCP-UBXD adaptor network identifies a role for UBXN10 in regulating ciliogenesis. Nat Cell Biol. 2015 Oct; 17(10):1356-69.

Citation

Raman M, Sergeev M, Garnaas M, Lydeard JR, Huttlin EL, Goessling W, Shah JV, Harper JW. 2015. Systematic proteomics of the VCP-UBXD adaptor network identifies a role for UBXN10 in regulating ciliogenesis. Nature cell biology. 17(10):1356-69. Pubmed: 26389662 DOI:10.1038/ncb3238

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.

Related Faculty

Wolfram Goessling, M.D., Ph.D.

Wolfram Goessling uses the zebrafish model to study regulators of liver development and to explore endodermal progenitor cell specification, organ differentiation, and growth.