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@ARTICLE{Siegert:155735,
      author       = {Siegert, Anna and Rankovic, Marija and Favretto, Filippo
                      and Ukmar-Godec, Tina and Strohäker, Timo and Becker,
                      Stefan and Zweckstetter, Markus},
      title        = {{I}nterplay between tau and α-synuclein liquid-liquid
                      phase separation.},
      journal      = {Protein science},
      volume       = {30},
      number       = {7},
      issn         = {1469-896X},
      address      = {Bethesda, Md.},
      publisher    = {Protein Society},
      reportid     = {DZNE-2021-00903},
      pages        = {1326 - 1336},
      year         = {2021},
      abstract     = {In Parkinson's disease with dementia, up to $50\%$ of
                      patients develop a high number of tau-containing
                      neurofibrillary tangles. Tau-based pathologies may thus act
                      synergistically with the α-synuclein pathology to confer a
                      worse prognosis. A better understanding of the relationship
                      between the two distinct pathologies is therefore required.
                      Liquid-liquid phase separation (LLPS) of proteins has
                      recently been shown to be important for protein aggregation
                      involved in amyotrophic lateral sclerosis, whereas tau phase
                      separation has been linked to Alzheimer's disease. We
                      therefore investigated the interaction of α-synuclein with
                      tau and its consequences on tau LLPS. We find α-synuclein
                      to have a low propensity for both, self-coacervation and
                      RNA-mediated LLPS at pH 7.4. However, full-length but not
                      carboxy-terminally truncated α-synuclein efficiently
                      partitions into tau/RNA droplets. We further demonstrate
                      that Cdk2-phosphorylation promotes the concentration of tau
                      into RNA-induced droplets, but at the same time decreases
                      the amount of α-synuclein inside the droplets. NMR
                      spectroscopy reveals that the interaction of the
                      carboxy-terminal domain of α-synuclein with the
                      proline-rich region P2 of tau is required for the
                      recruitment of α-synuclein into tau droplets. The combined
                      data suggest that the concentration of α-synuclein into
                      tau-associated condensates can contribute to synergistic
                      aSyn/tau pathologies.},
      keywords     = {Alzheimer Disease: metabolism / Amyotrophic Lateral
                      Sclerosis: metabolism / Humans / Recombinant Proteins:
                      chemistry / Recombinant Proteins: isolation $\&$
                      purification / Recombinant Proteins: metabolism /
                      alpha-Synuclein: chemistry / alpha-Synuclein: isolation $\&$
                      purification / alpha-Synuclein: metabolism / tau Proteins:
                      chemistry / tau Proteins: isolation $\&$ purification / tau
                      Proteins: metabolism / LLPS (Other) / phosphorylation
                      (Other) / tau (Other) / truncation (Other) / α-synuclein
                      (Other)},
      cin          = {AG Zweckstetter / Göttingen common},
      ddc          = {610},
      cid          = {I:(DE-2719)1410001 / I:(DE-2719)6000014},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33452693},
      pmc          = {pmc:PMC8197422},
      doi          = {10.1002/pro.4025},
      url          = {https://pub.dzne.de/record/155735},
}