Argonaute-mediated cytoplasmic lattice-assembling as a ubiquitin-safebox for proteostasis stiffness in oocytes
摘要
Oocytes are exceptionally long-lived cells and need to accumulate substantial cytoplasm during growth to support early embryonic development. Over their extended lifespan, protein degradation poses a constant threat to intracellular homeostasis, yet the protective mechanisms counteracting degradation remain poorly understood. Here we show that the oocyte-specific fibrous structure, cytoplasmic lattices (CPLs), functions as a tandem ubiquitin "safebox" that shields maternal proteins from ubiquitin-mediated proteolysis. By sequestering key soluble ubiquitin-conjugating enzymes and ubiquitin ligases within their highly stable architecture, assembled CPLs enable long-term suppression of K48-linked ubiquitination. We identify Argonaute AGO2 as a critical regulator of CPL assembly: by inhibiting proteasome activity, AGO2 allows efficient accumulation of CPL components during early assembly stages, thereby promoting the formation of a fully assembled, proteasome-resistant CPL structure. Integrated proteomic and functional analyses reveal that the release of four ubiquitination regulators-previously sequestered within CPLs-underlies maternal protein remodeling and early embryonic arrest upon CPL disassembly. Together, Argonaute-mediated CPL assembly represents a novel ubiquitin-suppressive strategy. We speculate that the exceptional stability of CPL precisely provides a crucial safeguard for maintaining robust protein homeostasis in oocytes during their prolonged life.
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