Architecture is critical for organelle function. The lengths of centrioles, key components of centrosomes, are tightly regulated. We adapted centrosome purification approaches to measure centrosomal protein phosphorylation. Centrosome-specific phosphoproteomics with and without cyclin-dependent kinase 1 (CDK1) activity revealed that CDK1 phosphorylates many centriolar proteins involved in centriole length control, including Centrobin. CDK1 regulated centriole length synergistically with CEP97-CCP110, a local centriolar complex. CEP97 restricted Centrobin localization to centrioles, whereas CDK1-dependent phosphorylation suppressed Centrobin's ability to promote centriole elongation. Thus, CDK1 and CEP97-CCP110 both restrict centriole elongation by inhibiting the function of Centrobin, a centriole elongation factor, but via different mechanisms. Overelongated centrioles failed to support ciliogenesis in human cells and in mouse embryos. Removing CEP97 during mouse development caused centriole overelongation, impaired ciliogenesis and attenuated Hedgehog (HH) signaling, disrupting mouse heart development. We conclude that CEP97-CCP110 and CDK1 cooperatively restrict Centrobin function to control centriole length, critical for mammalian development.
Liu et al. (Fri,) studied this question.