GoKawiilMammalian oocytes are filled by fibric structure called cytoplasmic lattice (CPL), essential for oocyte maturation and early embryonic development1-3. CPL comprises subcortical maternal complex (SCMC) and multiple components, including PADI62,4,5. Despite its discovery in the 1960s, the molecular architecture and assembly mechanisms of CPL have remained poorly understood. Here we present the cryo-electron microscopy (cryo-EM) structure of the CPL isolated from mouse oocytes. Our analysis identified 14 constitutive protein subunits and revealed that CPL is composed of repeating “U-shaped basket” (UB) and “adapter ring” (AR)- featured units, forming a filamentous architecture. AR adopts a two-fold symmetric conformation, containing two NLRP4f, four SCMC and two ZBED3 subunits circularized via two distinct interaction clusters. The UB is anchored by PADI6, a didecamer composed of ten homodimers assembled by two back-to-back pentamers, each forming the lateral side of UB. The underfoot base and up-down sides of the UB are formed by multiple central-symmetric assemblies (UBE2D3-UHRF1-NLRP14) and (TUBB2B-TUBB2A-FBXW24-SKP1) respectively, associating with the PADI6 pentamers to construct the intact UB structure. Two SCMC dimer within each AR connect the up and down sides of two adjacent UBs with an extensive protein-protein interaction network and thus maintain the repetitive connection between the neighboring CPL units. Our work unveils the architectural principles underlying the assembly of this large, periodic CPL filament, offering a molecular basis for understanding CPL’s functions in early mammalian embryogenesis and female reproductive disorders.
Molecular basis of oocyte cytoplasmic lattice assembly
Why This Matters
This study uncovers the detailed molecular architecture of the cytoplasmic lattice (CPL) in mammalian oocytes, revealing how its complex protein components assemble into a filamentous structure essential for early embryonic development. Understanding the CPL's assembly provides critical insights into female reproductive health and potential causes of infertility. These findings could pave the way for targeted interventions in reproductive disorders and improve assisted reproductive technologies.
Key Takeaways
- The cryo-EM structure identified 14 key protein subunits forming the CPL.
- CPL's architecture consists of repeating U-shaped baskets and adapter rings, crucial for its stability.
- Insights into CPL assembly may inform treatments for reproductive disorders and enhance fertility therapies.
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