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Redeployment of Archaeal ESCRT Systems Reveals Conserved Mechanisms Underlying Eukaryotic Complexity

Naripogu, K. B.; Tee, Y. H.; Senju, Y.; Li, H.; Bershadsky, A.; Honda, T.; Robinson, R. C.

2025-11-03 evolutionary biology
10.1101/2025.11.01.685982 bioRxiv
Show abstract

Eukaryotic ESCRT complexes remodel membranes at the plasma membrane and internal compartments, yet how these systems evolved from prokaryotic precursors functioning at the cellular membrane remains unresolved. Here, we show that ESCRT-II, ESCRT-III, VPS4, and ubiquitin from Candidatus Prometheoarchaeum syntrophicum (MK-D1), an Asgard archaeon closely related to eukaryotes, are recruited to canonical ESCRT sites in human cells, including centrosomes, midbodies, nuclear envelopes, endosomes despite the absence of these structures from MK-D1 morphology. In addition to MK-D1 ESCRT II recruitment at these regions, MK-D1 ESCRT-III and VPS4 form ring assemblies at midbodies and target reforming nuclear envelope regions. Futhermore, expression of MK-D1 ESCRT modules enhances efficiency of viral budding in human cells. These findings provide direct experimental evidence that archaeal ESCRT modules integrate into diverse eukaryotic structures, supporting a model in which ancestral membrane-remodeling systems were redeployed during eukaryogenesis to organize novel internal architectures.

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