Zentrum für Molekulare Biologie der Universität Heidelberg, Deutsches Krebsforschungszentrum-ZMBH Allianz, Universität Heidelberg, Heidelberg, Germany.
Heidelberg Biosciences International Graduate School (HBIGS), Universität Heidelberg, Heidelberg, Germany.
EMBO Rep. 2022 Jul 5;23(7):e53805. doi: 10.15252/embr.202153805. Epub 2022 May 23.
The centrosome linker component C-Nap1 (encoded by CEP250) anchors filaments to centrioles that provide centrosome cohesion by connecting the two centrosomes of an interphase cell into a single microtubule organizing unit. The role of the centrosome linker during development of an animal remains enigmatic. Here, we show that male CEP250 mice are sterile because sperm production is abolished. Premature centrosome separation means that germ stem cells in CEP250 mice fail to establish an E-cadherin polarity mark and are unable to maintain the older mother centrosome on the basal site of the seminiferous tubules. This failure prompts premature stem cell differentiation in expense of germ stem cell expansion. The concomitant induction of apoptosis triggers the complete depletion of germ stem cells and consequently infertility. Our study reveals a role for centrosome cohesion in asymmetric cell division, stem cell maintenance, and fertility.
中心体连接组件 C-Nap1（由 CEP250 编码）将纤维固定在中心体上，通过将间期细胞的两个中心体连接成一个微管组织单元，提供中心体的内聚力。中心体连接在动物发育过程中的作用仍然是个谜。在这里，我们发现雄性 CEP250 小鼠是不育的，因为精子的产生被废除了。过早的中心体分离意味着 CEP250 小鼠中的生殖干细胞无法建立 E-钙粘蛋白极性标记，并且无法在生精小管的基底部位维持较老的母中心体。这种失败促使干细胞过早分化，以牺牲生殖干细胞的扩增为代价。同时诱导的细胞凋亡触发了生殖干细胞的完全耗尽，进而导致不育。我们的研究揭示了中心体内聚力在不对称细胞分裂、干细胞维持和生育能力中的作用。
