biostudies-literatureHochmair JGemeinnützige Hertie-StiftungDeutsche ForschungsgemeinschaftDeutsches Zentrum für Neurodegenerative ErkrankungenBrightFocus Foundatione108882https://www.ebi.ac.uk/biostudies/studies/S-EPMC9156969biostudies-literatureUnknown41(11)Biomolecular condensation of the neuronal microtubule-associated protein Tau (MAPT) can be induced by coacervation with polyanions like RNA, or by molecular crowding. Tau condensates have been linked to both functional microtubule binding and pathological aggregation in neurodegenerative diseases. We find that molecular crowding and coacervation with RNA, two conditions likely coexisting in the cytosol, synergize to enable Tau condensation at physiological buffer conditions and to produce condensates with a strong affinity to charged surfaces. During condensate-mediated microtubule polymerization, their synergy enhances bundling and spatial arrangement of microtubules. We further show that different Tau condensates efficiently induce pathological Tau aggregates in cells, including accumulaThe EMBO journalMolecular crowding and RNA synergize to promote phase separation, microtubule interaction, and seeding of Tau condensates.PMC9156969402723784EXC 2056Falke SKraushar MLWegmann SDiez LBetzel CRadbruch HHochmair JKaniyappan SBrognaro HDominguez-Baquero AMandelkow EFranck MMielke TExner CfalseMolecular crowding and RNA synergize to promote phase separation, microtubule interaction, and seeding of Tau condensates.Biomolecular condensation of the neuronal microtubule-associated protein Tau (MAPT) can be induced by coacervation with polyanions like RNA, or by molecular crowding. Tau condensates have been linked to both functional microtubule binding and pathological aggregation in neurodegenerative diseases. We find that molecular crowding and coacervation with RNA, two conditions likely coexisting in the cytosol, synergize to enable Tau condensation at physiological buffer conditions and to produce condensates with a strong affinity to charged surfaces. During condensate-mediated microtubule polymerization, their synergy enhances bundling and spatial arrangement of microtubules. We further show that different Tau condensates efficiently induce pathological Tau aggregates in cells, including accumula2022-01-01T00:00:00Z2022 Jun2026-05-27T20:31:49.446Z2025-02-19T02:44:27.485ZS-EPMC91569693529809010.15252/embj.2021108882