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

Gagan D Gupta; Étienne Coyaud; João Gonçalves; Bahareh A Mojarad; Yi Liu; Qianzhu Wu; Ladan Gheiratmand; David Comartin; Johnny M Tkach; Sally W T Cheung; Mikhail Bashkurov; Monica Hasegan; James D Knight; Zhen-Yuan Lin; Markus Schueler; Friedhelm Hildebrandt; Jason Moffat; Anne-Claude Gingras; Brian Raught; Laurence Pelletier

doi:10.1016/j.cell.2015.10.065

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.

Authors

Gagan D Gupta¹, Étienne Coyaud², João Gonçalves¹, Bahareh A Mojarad³, Yi Liu³, Qianzhu Wu³, Ladan Gheiratmand¹, David Comartin³, Johnny M Tkach¹, Sally W T Cheung¹, Mikhail Bashkurov¹, Monica Hasegan¹, James D Knight¹, Zhen-Yuan Lin¹, Markus Schueler⁴, Friedhelm Hildebrandt⁴, Jason Moffat⁵, Anne-Claude Gingras³, Brian Raught⁶, Laurence Pelletier⁷

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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biotinylation
Cell Cycle
Centrosome / metabolism*
Cilia / metabolism*
Humans
Microtubule-Organizing Center / metabolism
Protein Interaction Maps*

Abstract

Publication types

MeSH terms

Grants and funding