Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156, Oeiras, Portugal.
iNOVA4Health | NOVA Medical School | Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal.
EMBO Rep. 2024 Jan;25(1):102-127. doi: 10.1038/s44319-023-00020-6. Epub 2024 Jan 10.
Centrioles are part of centrosomes and cilia, which are microtubule organising centres (MTOC) with diverse functions. Despite their stability, centrioles can disappear during differentiation, such as in oocytes, but little is known about the regulation of their structural integrity. Our previous research revealed that the pericentriolar material (PCM) that surrounds centrioles and its recruiter, Polo kinase, are downregulated in oogenesis and sufficient for maintaining both centrosome structural integrity and MTOC activity. We now show that the expression of specific components of the centriole cartwheel and wall, including ANA1/CEP295, is essential for maintaining centrosome integrity. We find that Polo kinase requires ANA1 to promote centriole stability in cultured cells and eggs. In addition, ANA1 expression prevents the loss of centrioles observed upon PCM-downregulation. However, the centrioles maintained by overexpressing and tethering ANA1 are inactive, unlike the MTOCs observed upon tethering Polo kinase. These findings demonstrate that several centriole components are needed to maintain centrosome structure. Our study also highlights that centrioles are more dynamic than previously believed, with their structural stability relying on the continuous expression of multiple components.
中心体是中心粒和纤毛的组成部分,它们是具有多种功能的微管组织中心(MTOC)。尽管中心体很稳定,但在分化过程中,如在卵母细胞中,它们可以消失,但对于它们结构完整性的调节知之甚少。我们之前的研究表明,围绕中心体的中心粒周围物质(PCM)及其招募者 Polo 激酶在卵发生过程中下调,足以维持中心体结构完整性和 MTOC 活性。我们现在表明,中心粒轮辐和壁的特定成分的表达对于维持中心体完整性是必不可少的。我们发现 Polo 激酶需要 ANA1 来促进培养细胞和卵子中中心体的稳定性。此外,ANA1 的表达可防止观察到的 PCM 下调时中心体的丢失。然而,过表达和固定 ANA1 维持的中心体是无活性的,与固定 Polo 激酶观察到的 MTOC 不同。这些发现表明,维持中心体结构需要几种中心粒成分。我们的研究还表明,中心体比以前认为的更具动态性,其结构稳定性依赖于多个成分的持续表达。