title: A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface.
abstract: The centrosome is the primary microtubule organizing center of the cells and templates the formation of cilia, thereby operating at a nexus of critical cellular functions. Here, we use proximity-dependent biotinylation (BioID) to map the centrosome-cilium interface; with 58 bait proteins we generate a protein topology network comprising >7,000 interactions. Analysis of interaction profiles coupled with high resolution phenotypic profiling implicates a number of protein modules in centriole duplication, ciliogenesis, and centriolar satellite biogenesis and highlights extensive interplay between these processes. By monitoring dynamic changes in the centrosome-cilium protein interaction landscape during ciliogenesis, we also identify satellite proteins that support cilia formation. Systematic profiling of proximity interactions combined with functional analysis thus provides a rich resource for better understanding human centrosome and cilia biology. Similar strategies may be applied to other complex biological structures or pathways.
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
authors.forename: Gagan D
authors.initials: GD
authors.lastname: Gupta
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, ON M5G 1L7, Canada.
authors.forename: Étienne
authors.initials: É
authors.lastname: Coyaud
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
authors.forename: João
authors.initials: J
authors.lastname: Gonçalves
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Bahareh A
authors.initials: BA
authors.lastname: Mojarad
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Qianzhu
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
authors.forename: Ladan
authors.initials: L
authors.lastname: Gheiratmand
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Comartin
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
authors.forename: Johnny M
authors.initials: JM
authors.lastname: Tkach
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
authors.forename: Sally W T
authors.initials: SW
authors.lastname: Cheung
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Bashkurov
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
authors.forename: Monica
authors.initials: M
authors.lastname: Hasegan
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
authors.forename: James D
authors.initials: JD
authors.lastname: Knight
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
authors.forename: Zhen-Yuan
authors.initials: ZY
authors.lastname: Lin
authors.affiliation: Division of Nephrology, Department of Medicine, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
authors.forename: Markus
authors.initials: M
authors.lastname: Schueler
authors.affiliation: Division of Nephrology, Department of Medicine, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Hildebrandt
authors.affiliation: Donnelly Centre and Banting and Best Department of Medical Research, University of Toronto, 160 College Street, Toronto, ON M5S 1A8, Canada.
authors.forename: Jason
authors.initials: J
authors.lastname: Moffat
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Anne-Claude
authors.initials: AC
authors.lastname: Gingras
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada. Electronic address: brian.raught@uhnres.utoronto.ca.
authors.forename: Brian
authors.initials: B
authors.lastname: Raught
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: pelletier@lunenfeld.ca.
authors.forename: Laurence
authors.initials: L
authors.lastname: Pelletier
mesh_terms: D019921:Biotinylation; D002453:Cell Cycle; D018385:Centrosome / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism*; D006801:Humans; D022101:Microtubule-Organizing Center / Q000378:metabolism; D060066:Protein Interaction Maps