Résumé
Centriolar satellites are membrane-less structures that function as key regulators of primary ciliumbiogenesis and ciliary signaling. As such, mutations affecting a number of satellite components causeciliopathies including retinal degeneration. To better understand these disease connections, it isnecessary to address two important questions: 1) How are satellites assembled, maintained anddynamically altered?; 2) What are the mechanisms by which satellites regulate cilium assembly andciliary signaling? In this project, we addressed these questions through dissecting the relationshipbetween the essential satellite scaffolding protein PCM1, microtubules and the tubulin glutamylaseTTLL5. Proteomic mapping of centriolar satellites identified interactions with TTLL tubulin glutamylases,which add glutamate residues to substrates to regulate their functional adaptation. Among TTLL family,we focused on TTLL5 because it is known that distribution of TTLL5 gene is associated with retinaldystrophies. Unbiased proteomic screen of TTLL5 identified components of the centriolar satellitesincluding PCM1. We showed that PCM1 is a substrate of TTLL5-dependent polyglutamylation, which canbe reversed by members of the CCP family. We show that polyglutamylation of PCM1 is required tomaintain centriolar satellite integrity. In line with that, glutamylation deficient PCM1 is likely tocontribute to the ciliogenesis and ciliary defects. Given that both TTLL5 and satellites are implicated inretinal degeneration and ciliopathies, glutamylation of centriolar satellites might be one the molecularmechanism underlying of these diseases.