Cytoplasmic lattices are megadalton storage complexes in mammalian oocytes

• 成果类型: Article
• 署名作者: Kilic, Zeynep Ilgin; van Loenhout, Joyce; Chaillet, Marten; van Es, Robert M.; Sobrevals Alcaraz, Paula; Vos, Harmjan R.; Noteborn, Willem E. M.; Leung, Miguel Ricardo
• 署名单位: Royal Netherlands Academy of Arts & Sciences; Hubrecht Institute (KNAW); Utrecht University; Utrecht University Medical Center; Utrecht University; Utrecht University Medical Center; Leiden University; Leiden University - Excl LUMC
• 刊物名称: NATURE
• ISSN/ISSBN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-026-10513-8
• 发表日期: 2026-06-11
• 页码: 41986725
• 关键词: SUBCORTICAL MATERNAL COMPLEX; cryo-em; CYTOSKELETAL ELEMENTS; embryonic-development; structural basis; eggs; crystallography; RECOGNITION; localizes; network

摘要

Mammalian oocytes store proteins for embryonic development on abundant structures called 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 modelling to reveal the molecular architecture and protein composition of native CPLs from mouse oocytes. We find that CPLs are formed by at least 13 different proteins that assemble into a megadalton-scale complex, including multiple copies of maternal effect factors such as PADI6 and the subcortical maternal complex. We show that proteins that are essential for early embryonic development are structural components of the CPLs, including the cytoskeletal proteins alpha-tubulin and beta-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 adapters. This represents an elegant molecular mechanism by which oocytes stockpile vital proteins through direct incorporation into highly stable supramolecular assemblies. Our findings provide a structural framework for understanding how disrupting stored maternal factors leads to infertility and developmental defects.