GoKawiilThe fertilized egg relies almost entirely on maternal stores in the oocyte to ensure the successful initiation of development1. The cytoplasmic lattices (CPLs) in mammalian oocytes store maternal-expressed proteins and play an essential role in embryogenesis2,3. Impairing multiple CPL members leads to early embryonic arrest (EEA), resulting in infertility in mammals. However, the mechanism underlying the assembly and storage of CPLs remains largely unknown. Here, we report the cryo-EM structure of a native mouse CPL repeating unit (~ 4 MDa) at 3.74 Å resolution. This repeating unit exhibits a tripartite architecture comprising a framework, extended linkers, and a CPL core. The external framework is built from PADI6 decamers and the subcortical maternal complexes (SCMC). Two linkers formed by NLRP4F polymerize the frameworks into an extended filament. In CPL core, the epigenetic regulator UHRF1 is trapped by PADI6, UBE2D, and NLRP14 in a compact, autoinhibited conformation that prevents nuclear entry and ubiquitin ligase activity. Moreover, the CPL core stores GTP-bound α/β-tubulin heterodimers and inactive SCF E3-ubiquitin ligase components (FBXW-SKP1 complex) in a poised but restrained state. These features establish CPLs as a dynamic regulatory pool that enables rapid microtubule assembly and tightly controlled ubiquitination during the oocyte-to-embryo transition. Together, this semi-in-situ structure illuminates CPL assembly and storage-module organization, and establishes CPLs as specialized proteostasis organelles for maternal regulation in oocytes and early embryonic development.
Structure of the mouse cytoplasmic lattice
Why This Matters
This groundbreaking cryo-EM study reveals the detailed structure of mouse cytoplasmic lattices (CPLs), key organelles that store maternal proteins essential for early embryonic development. Understanding CPL architecture and function offers insights into fertility and embryogenesis, potentially guiding future reproductive therapies and interventions. The findings highlight CPLs as critical regulators of proteostasis during the oocyte-to-embryo transition, with implications for both basic biology and clinical applications in reproductive health.
Key Takeaways
- Cryo-EM structure of mouse CPLs at 3.74 Å resolution reveals their tripartite architecture.
- CPLs store proteins like UHRF1 and tubulin, regulating early embryonic processes.
- Disruptions in CPL components can cause infertility due to early embryonic arrest.
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