Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA.
Cell and Developmental Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Curr Biol. 2023 Oct 9;33(19):4202-4216.e9. doi: 10.1016/j.cub.2023.08.075. Epub 2023 Sep 19.
Proper centrosome number and function relies on the accurate assembly of centrioles, barrel-shaped structures that form the core duplicating elements of the organelle. The growth of centrioles is regulated in a cell cycle-dependent manner; while new daughter centrioles elongate during the S/G2/M phase, mature mother centrioles maintain their length throughout the cell cycle. Centriole length is controlled by the synchronized growth of the microtubules that ensheathe the centriole barrel. Although proteins exist that target the growing distal tips of centrioles, such as CP110 and Cep97, these proteins are generally thought to suppress centriolar microtubule growth, suggesting that distal tips may also contain unidentified counteracting factors that facilitate microtubule polymerization. Currently, a mechanistic understanding of how distal tip proteins balance microtubule growth and shrinkage to either promote daughter centriole elongation or maintain centriole length is lacking. Using a proximity-labeling screen in Drosophila cells, we identified Cep104 as a novel component of a group of evolutionarily conserved proteins that we collectively refer to as the distal tip complex (DTC). We found that Cep104 regulates centriole growth and promotes centriole elongation through its microtubule-binding TOG domain. Furthermore, analysis of Cep104 null flies revealed that Cep104 and Cep97 cooperate during spermiogenesis to align spermatids and coordinate individualization. Lastly, we mapped the complete DTC interactome and showed that Cep97 is the central scaffolding unit required to recruit DTC components to the distal tip of centrioles.
中心体的数量和功能正常依赖于中心粒的精确组装,中心粒是形成细胞器复制元件的桶状结构。中心粒的生长在细胞周期中受到调节;新的子中心粒在 S/G2/M 期伸长,而成熟的母中心粒在整个细胞周期中保持其长度。中心粒长度受围绕中心粒桶生长的微管同步生长的控制。虽然存在靶向中心粒远端尖端的蛋白质,如 CP110 和 Cep97,但这些蛋白质通常被认为抑制中心粒微管生长,这表明远端尖端可能还含有促进微管聚合的未识别拮抗因子。目前,对于远端尖端蛋白如何平衡微管生长和收缩以促进子中心粒伸长或维持中心粒长度的机制理解还很缺乏。我们在果蝇细胞中使用邻近标记筛选,鉴定 Cep104 为一组进化保守蛋白的新成分,我们将其统称为远端尖端复合物(DTC)。我们发现 Cep104 通过其微管结合 TOG 结构域调节中心粒生长并促进中心粒伸长。此外,对 Cep104 缺失果蝇的分析表明,Cep104 和 Cep97 在精子发生过程中合作,使精原细胞对齐并协调个体化。最后,我们绘制了完整的 DTC 相互作用组,并表明 Cep97 是将 DTC 成分募集到中心粒远端尖端所必需的中央支架单元。