PUBLICATION

The centriolar satellite proteins Cep72 and Cep290 interact and are required for recruitment of BBS proteins to the cilium

Authors
Stowe, T.R., Wilkinson, C.J., Iqbal, A., and Stearns, T.
ID
ZDB-PUB-120709-4
Date
2012
Source
Molecular biology of the cell   23(17): 3322-3335 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • 3T3 Cells
  • Animals
  • Bardet-Biedl Syndrome
  • Cell Cycle Proteins/genetics
  • Cell Cycle Proteins/metabolism
  • Cell Line
  • Centrioles/genetics
  • Centrioles/metabolism
  • Centrosome
  • Cilia/metabolism*
  • Humans
  • Mice
  • Microtubule-Associated Proteins/genetics
  • Microtubule-Associated Proteins/metabolism*
  • Proteins/metabolism*
  • RNA Interference
  • RNA, Small Interfering
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
22767577 Full text @ Mol. Biol. Cell
Abstract

Defects in centrosome and cilium function are associated with phenotypically related syndromes called ciliopathies. Centriolar satellites are centrosome-associated structures, defined by the protein PCM1, that are implicated in centrosomal protein trafficking. We identify Cep72 as a PCM1-interacting protein required for recruitment of the ciliopathy-associated protein, Cep290, to centriolar satellites. Loss of centriolar satellites by depletion of PCM1 causes relocalization of Cep72 and Cep290 from satellites to the centrosome, suggesting that their association with centriolar satellites normally restricts their centrosomal localization. We identify interactions between PCM1, Cep72 and Cep290 and find that disruption of centriolar satellites by overexpression of Cep72 results in specific aggregation of these proteins and the BBSome component, BBS4. During ciliogenesis, BBS4 relocalizes from centriolar satellites to the primary cilium. This relocalization occurs normally in the absence of centriolar satellites (PCM1 depletion), but is impaired by depletion of Cep290 or Cep72, resulting in defective ciliary recruitment of the BBSome subunit BBS8. We propose that Cep290 and Cep72 in centriolar satellites regulate the ciliary localization of BBS4, which in turn affects assembly and recruitment of the BBSome. Finally, we show that loss of centriolar satellites in zebrafish leads to phenotypes consistent with cilium dysfunction and analogous to human ciliopathies.

Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Errata and Notes