荷兰皇家艺术与科学学院Miguel Ricardo Leung课题组近日取得一项新成果。经过不懈努力,他们的研究显示,细胞质晶格是哺乳动物卵母细胞中兆道尔顿级别的储存复合物。相关论文于2026年4月15日发表在《自然》杂志上。
课题组研究人员利用低温电子显微镜和基于人工智能的建模来阐明来自单母卵母细胞的天然CPLs的分子结构和蛋白质组成。课题组研究人员发现CPLs是由至少13种不同的蛋白质组装成一个兆子级复合体形成的,包括母体效应因子的多个拷贝,如PADI6和皮质下母体复合体(SCMC)。课题组研究人员发现,早期胚胎发育所必需的蛋白质实际上是CPLs的结构成分,包括细胞骨架蛋白α-和β-微管蛋白,它们作为未聚合的二聚体被纳入CPLs;以及一系列泛素化因子,如表观遗传调节因子和E3连接酶UHRF1,泛素结合E2酶和泛素连接酶底物接头。这代表了一种优雅的分子机制,卵母细胞通过直接结合到高度稳定的超分子组装中来储存重要的蛋白质。它们的结构解决了长达数十年的CPLs之谜,从而为理解破坏储存的母体因子如何导致不孕症和发育缺陷提供了一个结构框架。
据悉,哺乳动物卵母细胞在丰富的细胞质晶格(CPLs)上储存胚胎发育所需的蛋白质1;然而,他们实现这一目标的机制尚不清楚,很大程度上是因为晶格本身的分子组成是未知的。
附:英文原文
Title: Cytoplasmic lattices are megadalton storage complexes in mammalian oocytes
Author: Kl, Zeynep Ilgn, van Loenhout, Joyce, Chaillet, Marten, van Es, Robert M., Alcaraz, Paula Sobrevals, Vos, Harmjan R., Noteborn, Willem E. M., Leung, Miguel Ricardo
Issue&Volume: 2026-04-15
Abstract: Mammalian oocytes store proteins for embryonic development on abundant structures known as cytoplasmic lattices (CPLs)1; however, the mechanisms by which they achieve this are unclear, largely because the molecular composition of the lattices themselves is unknown. Here, we use cryo-electron microscopy and artificial intelligence-based modeling to elucidate the molecular architecture and protein composition of native CPLs from mouse oocytes. We find that CPLs are formed by at least 13 different proteins assembling into a megadalton-scale complex, including multiple copies of maternal effect factors such as PADI6 and the subcortical maternal complex (SCMC). We show that proteins essential for early embryonic development are in fact structural components of the CPLs, including the cytoskeletal proteins α- and β-tubulin, which are incorporated into CPLs as unpolymerized dimers; and an array of ubiquitination factors such as the epigenetic regulator and E3 ligase UHRF1, ubiquitin-conjugating E2 enzymes, and ubiquitin ligase substrate adaptors. This represents an elegant molecular mechanism by which oocytes stockpile vital proteins through direct incorporation into highly stable supramolecular assemblies. Our structures solve the decades-long mystery of the CPLs, thereby providing a structural framework for understanding how disrupting stored maternal factors leads to infertility and developmental defects.
DOI: 10.1038/s41586-026-10513-8
Source: https://www.nature.com/articles/s41586-026-10513-8
Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html
