Structure of the mouse cytoplasmic lattice

Area of Science:

• Cell Biology
• Developmental Biology
• Structural Biology

Background:

• Fertilized eggs depend on maternal stores within the oocyte for development.
• Cytoplasmic lattices (CPLs) in mammalian oocytes store maternal proteins essential for embryogenesis.
• Defects in CPLs cause early embryonic arrest and infertility, but their assembly and storage mechanisms are poorly understood.

Purpose of the Study:

• To elucidate the structural basis of cytoplasmic lattice (CPL) assembly and protein storage in mammalian oocytes.
• To understand the mechanism by which CPLs regulate maternal factors essential for the oocyte-to-embryo transition.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was used to determine the structure of a native mouse CPL repeating unit.
• High-resolution structural analysis (~3.74 Å) of the ~4 MDa CPL repeating unit.

Main Results:

• The CPL repeating unit has a tripartite architecture: a framework (PADI6, SCMC), linkers (NLRP4F), and a core.
• The CPL core sequesters the epigenetic regulator UHRF1 in an inactive state and stores GTP-bound tubulin and inactive SCF E3-ubiquitin ligase components.
• This organization allows CPLs to act as a dynamic regulatory pool for microtubule assembly and ubiquitination.

Conclusions:

• CPLs are specialized proteostasis organelles essential for maternal regulation during the oocyte-to-embryo transition.
• The determined structure reveals CPL assembly and the organization of storage modules, providing insights into their function in early embryonic development.
• CPLs ensure timely regulation of key proteins, preventing premature activity and enabling successful embryogenesis.