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 beta-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 beta-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.
authors: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors: Jantje M
authors: JM
authors: Gerdes
authors: Yangfan
authors: Y
authors: Liu
authors: Norann A
authors: NA
authors: Zaghloul
authors: Carmen C
authors: CC
authors: Leitch
authors: Shaneka S
authors: SS
authors: Lawson
authors: Masaki
authors: M
authors: Kato
authors: Philip A
authors: PA
authors: Beachy
authors: Philip L
authors: PL
authors: Beales
authors: George N
authors: GN
authors: DeMartino
authors: Shannon
authors: S
authors: Fisher
authors: Jose L
authors: JL
authors: Badano
authors: Nicholas
authors: N
authors: Katsanis
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002924:Ciliary Body / Q000378:metabolism*; D003593:Cytoplasm; D003599:Cytoskeleton / Q000737:chemistry / Q000648:ultrastructure; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D056385:Group II Chaperonins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008845:Microinjections; D008870:Microtubules / Q000378:metabolism*; D010641:Phenotype; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D051820:TCF Transcription Factors; D014158:Transcription, Genetic; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: C506279:Mkks protein, mouse; D061988:Proteasome Inhibitors; D051820:TCF Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D008156:Luciferases; D046988:Proteasome Endopeptidase Complex; D056385:Group II Chaperonins; D016547:Kinesins