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bioRxiv · 10.64898/2025.12.12.693869

The vault associates with membranes in situ

Geissler, K.·Kreysing, J. P.·Wang, Y.·Glushkova, D.·Obarska-Kosinska, A.·Hoffmann, P. C.·Böhm, S.·Schmidt, A.·Meier-Credo, J.·Langer, J.·Hummer, G.·Beck, M.
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Abstract

The eukaryotic vault particle is a giant ribonucleoprotein complex that assembles into an iconic barrel-like cage. Its cellular function has remained elusive despite extensive characterization. Using cryo-electron tomography of Dictyostelium discoideum cells, we define the distribution, structural states and interaction landscape of vault particles in situ. Surprisingly, we detect a subpopulation of vault particles associated with the endoplasmic reticulum (ER) and nuclear envelope membranes. This association occurs at a defined barrel height of the vault particle and at patches of reduced membrane bilayer thickness and altered curvature. We further find that a substantial fraction of vaults encloses 80S ribosomes in highly ordered orientations. These structural findings are further corroborated by proximity labeling experiments which identify ER-resident proteins and numerous ribosomal components as vault particle interactors. The membrane-bound and ribosome-encapsulating vault populations that we uncover will direct future studies towards revealing vault function.

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Geissler, K., Kreysing, J. P., Wang, Y., Glushkova, D., Obarska-Kosinska, A., Hoffmann, P. C., Böhm, S., Schmidt, A., Meier-Credo, J., Langer, J., Hummer, G., Beck, M.. 2025-12-15. The vault associates with membranes in situ. https://doi.org/10.64898/2025.12.12.693869

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