title: The MST1/2-SAV1 complex of the Hippo pathway promotes ciliogenesis.
abstract: Primary cilia are microtubule-based organelles that protrude from polarized epithelial cells. Although many structural and trafficking molecules that regulate ciliogenesis have been discovered, signalling proteins are not well defined. Here we show that the MST1/2-SAV1 complex, a core component of the Hippo pathway, promotes ciliogenesis. MST1 is activated during ciliogenesis and localizes to the basal body of cilia. Depletion of MST1/2 or SAV1 impairs ciliogenesis in cultured cells and induces ciliopathy phenotypes in zebrafish. MST1/2-SAV1 regulates ciliogenesis through two independent mechanisms: MST1/2 binds and phosphorylates Aurora kinase A (AURKA), leading to dissociation of the AURKA/HDAC6 cilia-disassembly complex; and MST1/2-SAV1 associates with the NPHP transition-zone complex, promoting ciliary localization of multiple ciliary cargoes. Our results suggest that components of the Hippo pathway contribute to establish a polarized cell structure in addition to regulating proliferation.
authors.affiliation: Department of Biological Sciences, National Creative Research Initiatives Center, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea.
authors.forename: Miju
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, National Creative Research Initiatives Center, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea.
authors.forename: Minchul
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Biology, Chungnam National University, Daejeon 305-764, Korea.
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Department of Biology, Chungnam National University, Daejeon 305-764, Korea.
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, National Creative Research Initiatives Center, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea.
authors.forename: Dae-Sik
authors.initials: DS
authors.lastname: Lim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D064096:Aurora Kinase A / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002923:Cilia / Q000502:physiology*; D003598:Cytoskeletal Proteins; D057809:HEK293 Cells; D000090683:Hippo Signaling Pathway; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000090742:Serine-Threonine Kinase 3; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000091102:YAP-Signaling Proteins; D015027:Zebrafish; D000099317:Hippo Kinases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D064096:Aurora Kinase A; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D000090742:Serine-Threonine Kinase 3; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000091102:YAP-Signaling Proteins; C108725:NPHP1 protein, human; C415864:SAV1 protein, human; C088374:YAP1 protein, human; C092745:LATS1 protein, human; C406449:LATS2 protein, human; C095566:STK4 protein, human; D000099317:Hippo Kinases; C576917:AURKA protein, human; C097835:STK3 protein, human; C433811:HDAC6 protein, human