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@ARTICLE{Hochmair:163787,
      author       = {Hochmair, Janine and Exner, Christian and Franck,
                      Maximilian and Dominguez-Baquero, Alvaro and Diez, Lisa and
                      Brognaro, Hévila and Kraushar, Matthew L and Mielke,
                      Thorsten and Radbruch, Helena and Kaniyappan,
                      Senthilvelrajan and Falke, Sven and Mandelkow, Eckhard and
                      Betzel, Christian and Wegmann, Susanne},
      title        = {{M}olecular crowding and {RNA} synergize to promote phase
                      separation, microtubule interaction, and seeding of {T}au
                      condensates},
      journal      = {The EMBO journal},
      volume       = {41},
      number       = {11},
      issn         = {0261-4189},
      address      = {Hoboken, NJ [u.a.]},
      publisher    = {Wiley},
      reportid     = {DZNE-2022-00525},
      pages        = {e108882},
      year         = {2022},
      note         = {(CC BY-NC-ND)},
      abstract     = {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 accumulations at the nuclear
                      envelope that correlate with nucleocytoplasmic transport
                      deficits. Fluorescent lifetime imaging reveals different
                      molecular packing densities of Tau in cellular accumulations
                      and a condensate-like density for nuclear-envelope Tau.
                      These findings suggest that a complex interplay between
                      interaction partners, post-translational modifications, and
                      molecular crowding regulates the formation and function of
                      Tau condensates. Conditions leading to prolonged existence
                      of Tau condensates may induce the formation of
                      seeding-competent Tau and lead to distinct cellular Tau
                      accumulations.},
      keywords     = {Humans / Microtubules: metabolism / Neurodegenerative
                      Diseases: metabolism / Neurons: metabolism / Protein Binding
                      / RNA: metabolism / tau Proteins: metabolism},
      cin          = {AG Wegmann / AG Mandelkow 1 / AG Mandelkow 2},
      ddc          = {570},
      cid          = {I:(DE-2719)1810006 / I:(DE-2719)1013014 /
                      I:(DE-2719)1013015},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC9156969},
      pubmed       = {pmid:35298090},
      doi          = {10.15252/embj.2021108882},
      url          = {https://pub.dzne.de/record/163787},
}