title: The PPFIA1-PP2A protein complex promotes trafficking of Kif7 to the ciliary tip and Hedgehog signaling.
abstract: The primary cilium is required for Hedgehog (Hh) signaling in vertebrates. Hh leads to ciliary accumulation and activation of the transmembrane protein Smoothened (Smo) and affects the localization of several pathway components, including the Gli family of transcriptional regulators, within different regions of primary cilia. Genetic analysis indicates that the kinesin protein Kif7 both promotes and inhibits mouse Hh signaling. Using mass spectrometry, we identified liprin-α1 (PPFIA1) and the protein phosphatase PP2A as Kif7-interacting proteins, and we showed that they were important for the trafficking of Kif7 and Gli proteins to the tips of cilia and for the transcriptional output of Hh signaling. Our results suggested that PPFIA1 functioned with PP2A to promote the dephosphorylation of Kif7, triggering Kif7 localization to the tips of primary cilia and promoting Gli transcriptional activity.
authors.affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada.
authors.forename: Yulu C
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
authors.forename: Amber L
authors.initials: AL
authors.lastname: Couzens
authors.affiliation: Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Ashish R
authors.initials: AR
authors.lastname: Deshwar
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
authors.forename: Linda D
authors.initials: LD
authors.lastname: B McBroom-Cerajewski
authors.affiliation: Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Vijitha
authors.initials: V
authors.lastname: Puviindran
authors.affiliation: Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada. Program in Developmental and Stem Cell Biology, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Scott
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada. Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Anne-Claude
authors.initials: AC
authors.lastname: Gingras
authors.affiliation: Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada. Program in Developmental and Stem Cell Biology, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Hui
authors.affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada. Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada. stephane.angers@utoronto.ca.
authors.forename: Stephane
authors.initials: S
authors.lastname: Angers
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002923:Cilia / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C400551:GLI1 protein, human; C498520:Gli1 protein, mouse; D053823:Hedgehog Proteins; C502069:KIF7 protein, human; D051741:Kruppel-Like Transcription Factors; C094398:PPFIA1 protein, human; C477798:Ppfia1 protein, mouse; D011506:Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; D000071676:Zinc Finger Protein GLI1; D054648:Protein Phosphatase 2; C543639:Kif7 protein, mouse; D016547:Kinesins