Article abstract
Nature Genetics 39, 1350 - 1360 (2007)
Published online: 30 September 2007 | doi:10.1038/ng.2007.12
Disruption of the basal body compromises proteasomal function and perturbs intracellular Wnt response
Jantje M Gerdes1, Yangfan Liu1, Norann A Zaghloul1, Carmen C Leitch1, Shaneka S Lawson1, Masaki Kato2,6, Philip A Beachy2,6, Philip L Beales3, George N DeMartino4, Shannon Fisher1, Jose L Badano1,5 & Nicholas Katsanis1,6,7
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 
-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 -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.
- McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
- Department of Developmental Biology, Institute for Stem Cell Biology and Regenerative Medicine, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA.
- Molecular Medicine Unit, Institute of Child Health, University College London, WC1N 1EH, UK.
- Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
- Institut Pasteur, CP11400 Montevideo, Uruguay.
- Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
- Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Correspondence to: Nicholas Katsanis1,6,7 e-mail: katsanis@jhmi.edu
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