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bioRxiv · 10.64898/2026.03.30.715190

The cytoplasmic lattice in mammalian eggs sequesters ubiquitination machinery and tubulin in reserve

Li, Y.·Zheng, W.·Leem, J.·Wu, C.·Tang, S.·Mogessie, B.·Xiong, Y.
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Abstract

The cytoplasmic lattice (CPL) in mammalian eggs is essential for early embryonic development, but its molecular components, structural organization, and functional capacity have remained elusive. Here, using cryo-electron microscopy, we show that the CPL filament in mouse eggs contains repeating units with a periodicity of [~]37 nm, and determine its high-resolution, native structure and complete subunit composition. The CPL architecture organizes maternal-effect proteins, ubiquitination machinery, and tubulin into a highly structured reservoir. Maternal-effect proteins form the scaffold of the CPL to sequester a UBE2D-UHRF1 E2-E3 ubiquitination module and three distinct FBXW E3 ubiquitin ligases, notably all in activity-excluded states. The CPL further contains an {beta}-tubulin heterodimer in a GTP-bound state with a calcium ion coordinated to -tubulin, suggesting microtubule assembly-competent tubulin held in reserve. The CPL structure is capped at each end by a terminal unit that lacks a PADI6 dimer, a scaffold component, thereby preventing further oligomerization. Interactions between maternal-effect proteins in adjacent CPL units promote the assembly of a three-dimensional lattice in the egg cytoplasm. Taken together, our work defines how CPL assembly and architecture prime mammalian eggs for ubiquitin-mediated protein degradation and cytoskeletal remodeling during the egg-to-embryo transition.

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Li, Y., Zheng, W., Leem, J., Wu, C., Tang, S., Mogessie, B., Xiong, Y.. 2026-04-01. The cytoplasmic lattice in mammalian eggs sequesters ubiquitination machinery and tubulin in reserve. https://doi.org/10.64898/2026.03.30.715190

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