Laboratory of Cellular and Developmental Signaling, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Cancer & Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
EMBO Rep. 2022 Apr 5;23(4):e52775. doi: 10.15252/embr.202152775. Epub 2022 Feb 24.
Motile cilia on the cell surface generate movement and directional fluid flow that is crucial for various biological processes. Dysfunction of these cilia causes human diseases such as sinopulmonary disease and infertility. Here, we show that Ccdc108, a protein linked to male infertility, has an evolutionarily conserved requirement in motile multiciliation. Using Xenopus laevis embryos, Ccdc108 is shown to be required for the migration and docking of basal bodies to the apical membrane in epidermal multiciliated cells (MCCs). We demonstrate that Ccdc108 interacts with the IFT-B complex, and the ciliation requirement for Ift74 overlaps with Ccdc108 in MCCs. Both Ccdc108 and IFT-B proteins localize to migrating centrioles, basal bodies, and cilia in MCCs. Importantly, Ccdc108 governs the centriolar recruitment of IFT while IFT licenses the targeting of Ccdc108 to the cilium. Moreover, Ccdc108 is required for the centriolar recruitment of Drg1 and activated RhoA, factors that help establish the apical actin network in MCCs. Together, our studies indicate that Ccdc108 and IFT-B complex components cooperate in multiciliogenesis.
细胞表面的游动纤毛产生运动和定向的流体流动，这对各种生物过程至关重要。这些纤毛的功能障碍会导致人类疾病，如肺-鼻疾病和不育。在这里，我们表明与男性不育有关的蛋白 Ccdc108 在多纤毛的运动中有一个进化保守的需求。利用非洲爪蟾胚胎，证明 Ccdc108 对于表皮多纤毛细胞 (MCCs) 中的基体向顶端膜的迁移和对接是必需的。我们证明 Ccdc108 与 IFT-B 复合物相互作用，并且 Ift74 的纤毛需求与 MCCs 中的 Ccdc108 重叠。Ccdc108 和 IFT-B 蛋白都定位于 MCCs 中的迁移中心体、基体和纤毛。重要的是，Ccdc108 控制着 IFT 对基体的募集，而 IFT 则将 Ccdc108 靶向纤毛。此外，Ccdc108 对于 Drg1 和激活的 RhoA 的中心体募集是必需的，这些因子有助于在 MCCs 中建立顶端肌动蛋白网络。总之，我们的研究表明 Ccdc108 和 IFT-B 复合物成分在多纤毛发生中合作。
