Disruption of the basal body compromises proteasomal function and perturbs intracellular Wnt response

Jantje M. Gerdes, Yangfan Liu, Norann A. Zaghloul, Carmen C. Leitch, Shaneka S. Lawson, Masaki Kato, Philip A. Beachy, Philip L. Beales, George N. DeMartino, Shannon Fisher, Jose L. Badano, Nicholas Katsanis

Research output: Contribution to journalArticle

283 Citations (Scopus)

Abstract

Primary cilia and basal bodies are evolutionarily conserved organelles that mediate communication between the intracellular and extracellular environments. Here we show that bbs1, bbs4 and mkks (also known as bbs6), which encode basal body proteins, are required for convergence and extension in zebrafish and interact with wnt11 and wnt5b. Suppression of bbs1, bbs4 and mkks transcripts results in stabilization of β-catenin with concomitant upregulation of T-cell factor (TCF)-dependent transcription in both zebrafish embryos and mammalian ciliated cells, a defect phenocopied by the silencing of the axonemal kinesin subunit KIF3A but not by chemical disruption of the cytoplasmic microtubule network. These observations are attributable partly to defective degradation by the proteasome; suppression of BBS4 leads to perturbed proteasomal targeting and concomitant accumulation of cytoplasmic β-catenin. Cumulatively, our data indicate that the basal body is an important regulator of Wnt signal interpretation through selective proteolysis and suggest that defects in this system may contribute to phenotypes pathognomonic of human ciliopathies.

Original languageEnglish (US)
Pages (from-to)1350-1360
Number of pages11
JournalNature Genetics
Volume39
Issue number11
DOIs
StatePublished - Nov 2007

Fingerprint

Basal Bodies
Catenins
Zebrafish
Mammalian Embryo
TCF Transcription Factors
Kinesin
Cilia
Proteasome Endopeptidase Complex
Microtubules
Organelles
Proteolysis
Up-Regulation
Communication
Phenotype
Proteins

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Gerdes, J. M., Liu, Y., Zaghloul, N. A., Leitch, C. C., Lawson, S. S., Kato, M., ... Katsanis, N. (2007). Disruption of the basal body compromises proteasomal function and perturbs intracellular Wnt response. Nature Genetics, 39(11), 1350-1360. https://doi.org/10.1038/ng.2007.12

Disruption of the basal body compromises proteasomal function and perturbs intracellular Wnt response. / Gerdes, Jantje M.; Liu, Yangfan; Zaghloul, Norann A.; Leitch, Carmen C.; Lawson, Shaneka S.; Kato, Masaki; Beachy, Philip A.; Beales, Philip L.; DeMartino, George N.; Fisher, Shannon; Badano, Jose L.; Katsanis, Nicholas.

In: Nature Genetics, Vol. 39, No. 11, 11.2007, p. 1350-1360.

Research output: Contribution to journalArticle

Gerdes, JM, Liu, Y, Zaghloul, NA, Leitch, CC, Lawson, SS, Kato, M, Beachy, PA, Beales, PL, DeMartino, GN, Fisher, S, Badano, JL & Katsanis, N 2007, 'Disruption of the basal body compromises proteasomal function and perturbs intracellular Wnt response', Nature Genetics, vol. 39, no. 11, pp. 1350-1360. https://doi.org/10.1038/ng.2007.12
Gerdes, Jantje M. ; Liu, Yangfan ; Zaghloul, Norann A. ; Leitch, Carmen C. ; Lawson, Shaneka S. ; Kato, Masaki ; Beachy, Philip A. ; Beales, Philip L. ; DeMartino, George N. ; Fisher, Shannon ; Badano, Jose L. ; Katsanis, Nicholas. / Disruption of the basal body compromises proteasomal function and perturbs intracellular Wnt response. In: Nature Genetics. 2007 ; Vol. 39, No. 11. pp. 1350-1360.
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