A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface

  • Cell. 2015 Dec 3;163(6):1484-99. doi: 10.1016/j.cell.2015.10.065.
Gagan D Gupta  1 ,  Étienne Coyaud  2 ,  João Gonçalves  1 ,  Bahareh A Mojarad  3 ,  Yi Liu  3 ,  Qianzhu Wu  3 ,  Ladan Gheiratmand  1 ,  David Comartin  3 ,  Johnny M Tkach  1 ,  Sally W T Cheung  1 ,  Mikhail Bashkurov  1 ,  Monica Hasegan  1 ,  James D Knight  1 ,  Zhen-Yuan Lin  1 ,  Markus Schueler  4 ,  Friedhelm Hildebrandt  4 ,  Jason Moffat  5 ,  Anne-Claude Gingras  3 ,  Brian Raught  6 ,  Laurence Pelletier  7
Affiliations
  • 1. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
  • 2. Princess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, ON M5G 1L7, Canada.
  • 3. 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.
  • 4. 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.
  • 5. Donnelly Centre and Banting and Best Department of Medical Research, University of Toronto, 160 College Street, Toronto, ON M5S 1A8, Canada.
  • 6. 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: [email protected].
  • 7. 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: [email protected].
PMID: 26638075 DOI: 10.1016/j.cell.2015.10.065
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.