@article{fe2641033740499b9b800532ba6ad9ec,
title = "Disruption of the basal body compromises proteasomal function and perturbs intracellular Wnt response",
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.",
author = "Gerdes, {Jantje M.} and Yangfan Liu and Zaghloul, {Norann A.} and Leitch, {Carmen C.} and Lawson, {Shaneka S.} and Masaki Kato and Beachy, {Philip A.} and Beales, {Philip L.} and DeMartino, {George N.} and Shannon Fisher and Badano, {Jose L.} and Nicholas Katsanis",
note = "Funding Information: We apologize to our colleagues whose work we were unable to cite because of a strict 50-reference limit. We thank J. Nathans, J. Axelrod, L. Menezes, G. Germino and E. Davis for their critical evaluation of this manuscript, and A. Gherman for the quantification of the western blots. We also thank J. Nathans for the gift of the 293T luciferase reporter cell line, J. Kitajewski for the mouse Wnt cDNAs, G. Walz for the gift of the Myr/Pal Dvl construct, B. Yoder for the gift of anti-polaris/IFT88 antibody and S. Leach for the validated b-catenin antibody. This work was supported by grants from the German Academic Exchange Service (J.G.), the Polycystic Kidney Disease Foundation (J.B.), the National Institute of Child Health and Development (N.K.), the National Institute of Diabetes, Digestive and Kidney disorders (N.K.), the National Institute for Arthritis and Musculoskeletal disorders (S.F.) and the Medical Research Council (P.L.B.). P.L.B. is a Senior Wellcome Trust Fellow. P.A.B. is an Investigator of the Howard Hughes Medical Institute.",
year = "2007",
month = nov,
doi = "10.1038/ng.2007.12",
language = "English (US)",
volume = "39",
pages = "1350--1360",
journal = "Nature genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "11",
}