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A nuclear TRiC/CCT chaperonin assembles meiotic HORMAD proteins into chromosome axes competent for crossing over

Zetka, M.; Pezeshki, A.; Jones, S. J.; Silva, N.

2025-03-03 cell biology
10.1101/2025.03.03.641182 bioRxiv
Show abstract

The meiotic chromosome axis organizes chromatin and sets the stage for homolog pairing and recombination. Meiotic HORMA domain proteins (mHORMADs) are conserved axis components that conformationally transform during target binding. In C. elegans, four functionally distinct mHORMADs directly interact, but how binding between them is restricted to axis assembly is unknown. Using a mutation in the mHORMADs that delays axis assembly, we isolated a suppressor mutation in a TRiC/CCT chaperonin subunit that restored mHORMAD localization. CCT-4 associates with meiotic chromatin and forms in vivo complexes with mHORMADs, while germline disruption of TRiC results in axis defects, indicating a nuclear function for TRiC alongside meiotic chromosomes. We propose that chromosome-tethered TRiC folds mHORMADs into a conformationally active local population required for axis morphogenesis. More broadly, our results support the model that spatially-restricted folding by TRiC/CCT is a mechanism of controlling the assembly of multimeric complexes that function in tightly co-ordinated events.

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