title: PTEN regulates cilia through Dishevelled.
abstract: Cilia are hair-like cellular protrusions important in many aspects of eukaryotic biology. For instance, motile cilia enable fluid movement over epithelial surfaces, while primary (sensory) cilia play roles in cellular signalling. The molecular events underlying cilia dynamics, and particularly their disassembly, are not well understood. Phosphatase and tensin homologue (PTEN) is an extensively studied tumour suppressor, thought to primarily act by antagonizing PI3-kinase signalling. Here we demonstrate that PTEN plays an important role in multicilia formation and cilia disassembly by controlling the phosphorylation of Dishevelled (DVL), another ciliogenesis regulator. DVL is a central component of WNT signalling that plays a role during convergent extension movements, which we show here are also regulated by PTEN. Our studies identify a novel protein substrate for PTEN that couples PTEN to regulation of cilia dynamics and WNT signalling, thus advancing our understanding of potential underlying molecular etiologies of PTEN-related pathologies.
authors.affiliation: Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
authors.forename: Iryna
authors.initials: I
authors.lastname: Shnitsar
authors.affiliation: Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Bashkurov
authors.affiliation: Protein and Nucleic Acid Chemistry Division, Medical Research Council Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
authors.forename: Glenn R
authors.identifier: http://orcid.org/0000-0002-1386-4719
authors.initials: GR
authors.lastname: Masson
authors.affiliation: Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
authors.forename: Abiodun A
authors.initials: AA
authors.lastname: Ogunjimi
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90095, USA.
authors.forename: Sherly
authors.initials: S
authors.lastname: Mosessian
authors.affiliation: Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
authors.forename: Eduardo Aguiar
authors.initials: EA
authors.lastname: Cabeza
authors.affiliation: Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
authors.forename: Calley L
authors.initials: CL
authors.lastname: Hirsch
authors.affiliation: Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
authors.forename: Daniel
authors.initials: D
authors.lastname: Trcka
authors.affiliation: Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
authors.forename: Gerald
authors.initials: G
authors.lastname: Gish
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90095, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Jiao
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90095, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada M5S 3G5.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Winklbauer
authors.affiliation: Protein and Nucleic Acid Chemistry Division, Medical Research Council Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
authors.forename: Roger L
authors.initials: RL
authors.lastname: Williams
authors.affiliation: Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.|Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
authors.forename: Laurence
authors.initials: L
authors.lastname: Pelletier
authors.affiliation: Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.|Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Wrana
authors.affiliation: Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
authors.forename: Miriam
authors.initials: M
authors.lastname: Barrios-Rodiles
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002923:Cilia / Q000378:metabolism*; D000072261:Dishevelled Proteins; D004625:Embryo, Nonmammalian; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D018613:Microscopy, Confocal; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D012160:Retina / Q000166:cytology; D060449:Wnt Signaling Pathway; D029867:Xenopus Proteins; D014982:Xenopus laevis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000606586:DVL1 protein, Xenopus; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D029867:Xenopus Proteins; D019869:Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase