Department of Molecular Biology and Genetics, Koç University, Istanbul, Turkey.
Department of Bioengineering, Imperial College London, London, UK.
J Cell Biol. 2023 Dec 4;222(12). doi: 10.1083/jcb.202305009. Epub 2023 Nov 7.
Centrioles are microtubule-based organelles responsible for forming centrosomes and cilia, which serve as microtubule-organizing, signaling, and motility centers. Biogenesis and maintenance of centrioles with proper number, size, and architecture are vital for their functions during development and physiology. While centriole number control has been well-studied, less is understood about their maintenance as stable structures with conserved size and architecture during cell division and ciliary motility. Here, we identified CCDC15 as a centriole protein that colocalizes with and interacts with the inner scaffold, a crucial centriolar subcompartment for centriole size control and integrity. Using ultrastructure expansion microscopy, we found that CCDC15 depletion affects centriole length and integrity, leading to defective cilium formation, maintenance, and response to Hedgehog signaling. Moreover, loss-of-function experiments showed CCDC15's role in recruiting both the inner scaffold protein POC1B and the distal SFI1/Centrin-2 complex to centrioles. Our findings reveal players and mechanisms of centriole architectural integrity and insights into diseases linked to centriolar defects.
中心体是微管为基础的细胞器，负责形成中心粒和纤毛，作为微管组织、信号和运动中心。中心体的生物发生和维持适当的数量、大小和结构对于其在发育和生理过程中的功能至关重要。虽然中心体数量的控制已经得到了很好的研究，但对于它们在细胞分裂和纤毛运动过程中作为具有保守大小和结构的稳定结构的维持，了解较少。在这里，我们鉴定了 CCDC15 作为一种中心体蛋白，它与内支架共定位并相互作用，内支架是一个对中心体大小控制和完整性至关重要的中心体亚区室。使用超微结构扩展显微镜，我们发现 CCDC15 的缺失会影响中心体的长度和完整性，导致纤毛形成、维持和对 Hedgehog 信号的反应缺陷。此外，功能丧失实验表明 CCDC15 可以招募内支架蛋白 POC1B 和远端 SFI1/Centrin-2 复合物到中心体。我们的发现揭示了中心体结构完整性的参与者和机制，并深入了解与中心体缺陷相关的疾病。
