A dynamic protein interaction landscape of the human centrosome-cilium interface

Summary

Centrioles coordinate the primary microtubule organizing center of the cell and template 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 >7000 interactions. Analysis of interaction profiles coupled with high resolution phenotypic profiling implicates a number of new 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.

Graphical abstract

We use in vivo proximity-dependent biotinylation(BioID) to generate a protein interaction map of the human centrosome-cilium interface. Avast and functionally rich interaction space is characterized, allowing us to uncover protein modules critical for centrosome and cilium biogenesis. We demonstrate pervasive interplay between centriole duplication, centriolar satellite biogenesis and ciliogenesis, anddiscover pronounced dynamic modulation of the protein interaction landscape during the ciologenesis program. Our work thus provides a rich resource for better understanding human centrosome and cilia biology.