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: brian.raught@uhnres.utoronto.ca.
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: pelletier@lunenfeld.ca.

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.

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