McIdas localizes at centrioles and controls centriole numbers through PLK4-dependent phosphorylation

ABSTRACT: The centriole duplication cycle must be tightly controlled and coordinated with the chromosome cycle to maintain a proper number of centrioles in cells. Aberrations in centriole biogenesis can lead to cancer, developmental disorders and ciliopathies, yet the molecular determinants of centriole number control and the link between the centrosome and chromosome cycles remain poorly characterized. Here, we show that McIdas -previously implicated in cell cycle control and centriole amplification in multiciliated cells- is critical to maintain a proper number of centrioles in proliferating cells. Using expansion microscopy, we demonstrate that McIdas is present at the middle part of centrioles, where it exhibits a differential localization from the mother to the daughter centriole as the cell cycle proceeds. Regulation of McIdas expression is critical for the maintenance of correct centriole number in normal and cancer cells. Loss of McIdas perturbs daughter centriole biogenesis and centrosomal SAS6 recruitment, whereas its ectopic overexpression induces centriole overduplication. Consistently, McIdas depletion reduces PLK4-induced centriole amplification. We further show that McIdas interacts with PLK4 and is a novel substrate of this kinase. Multiple PLK4-specific phosphorylation sites on McIdas protein were identified through tandem mass-spectrometry analysis and characterized as important for McIdas role on centriole duplication. Our results demonstrate that McIdas is localized at centrosomes and affects the core centriole duplication machinery. This novel, direct role of McIdas on centriole duplication could link its previously seemingly unrelated functions in the chromosome cycle and multiciliogenesis.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Mario Oroshi  

LAB HEAD: Matthias Mann

PROVIDER: PXD037043 | Pride | 2025-12-02

REPOSITORIES: Pride