Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Tokyo 113-0033, Japan.
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Tokyo 113-0033, Japan
Biol Open. 2021 Mar 3;10(3):bio056432. doi: 10.1242/bio.056432.
The deuterosome is a non-membranous organelle involved in large-scale centriole amplification during multiciliogenesis. Deuterosomes are specifically assembled during the process of multiciliogenesis. However, the molecular mechanisms underlying deuterosome formation are poorly understood. In this study, we investigated the molecular properties of deuterosome protein 1 (Deup1), an essential protein involved in deuterosome assembly. We found that Deup1 has the ability to self-assemble into macromolecular condensates both and in cells. The Deup1-containing structures formed in multiciliogenesis and the Deup1 condensates self-assembled showed low turnover of Deup1, suggesting that Deup1 forms highly stable structures. Our biochemical analyses revealed that an increase of the concentration of Deup1 and a crowded molecular environment both facilitate Deup1 self-assembly. The self-assembly of Deup1 relies on its N-terminal region, which contains multiple coiled coil domains. Using an optogenetic approach, we demonstrated that self-assembly and the C-terminal half of Deup1 were sufficient to spatially compartmentalize centrosomal protein 152 (Cep152) and polo like kinase 4 (Plk4), master components for centriole biogenesis, in the cytoplasm. Collectively, the present data suggest that Deup1 forms the structural core of the deuterosome through self-assembly into stable macromolecular condensates.This article has an associated First Person interview with the first author of the paper.
基体是参与多纤毛发生过程中中心粒大规模扩增的非膜细胞器。基体在多纤毛发生过程中特异性组装。然而，基体形成的分子机制尚不清楚。在这项研究中，我们研究了基体蛋白 1（Deup1）的分子特性，Deup1 是参与基体组装的必需蛋白。我们发现 Deup1 具有在 和细胞内自我组装成大分子凝聚物的能力。在多纤毛发生过程中形成的含有 Deup1 的结构和自我组装的 Deup1 凝聚物显示出 Deup1 低周转率，表明 Deup1 形成高度稳定的结构。我们的生化分析表明，Deup1 浓度的增加和拥挤的分子环境都有利于 Deup1 自组装。Deup1 的自组装依赖于其包含多个卷曲螺旋结构域的 N 端区域。通过光遗传学方法，我们证明了自我组装和 Deup1 的 C 端半部分足以在细胞质中对中心体蛋白 152（Cep152）和 Polo 样激酶 4（Plk4）进行空间分区，这两种蛋白是中心体生物发生的主要成分。总之，这些数据表明，Deup1 通过自我组装成稳定的大分子凝聚物形成基体的结构核心。本文有与论文第一作者的相关第一人称访谈。
