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001     155735
005     20230915092340.0
024 7 _ |a 10.1002/pro.4025
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024 7 _ |a pmid:33452693
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024 7 _ |a 1469-896X
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037 _ _ |a DZNE-2021-00903
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Siegert, Anna
|0 P:(DE-2719)9000764
|b 0
|e First author
245 _ _ |a Interplay between tau and α-synuclein liquid-liquid phase separation.
260 _ _ |a Bethesda, Md.
|c 2021
|b Protein Society
336 7 _ |a article
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336 7 _ |a Journal Article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a 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.
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650 _ 7 |a LLPS
|2 Other
650 _ 7 |a phosphorylation
|2 Other
650 _ 7 |a tau
|2 Other
650 _ 7 |a truncation
|2 Other
650 _ 7 |a α-synuclein
|2 Other
650 _ 2 |a Alzheimer Disease: metabolism
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: metabolism
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Recombinant Proteins: chemistry
|2 MeSH
650 _ 2 |a Recombinant Proteins: isolation & purification
|2 MeSH
650 _ 2 |a Recombinant Proteins: metabolism
|2 MeSH
650 _ 2 |a alpha-Synuclein: chemistry
|2 MeSH
650 _ 2 |a alpha-Synuclein: isolation & purification
|2 MeSH
650 _ 2 |a alpha-Synuclein: metabolism
|2 MeSH
650 _ 2 |a tau Proteins: chemistry
|2 MeSH
650 _ 2 |a tau Proteins: isolation & purification
|2 MeSH
650 _ 2 |a tau Proteins: metabolism
|2 MeSH
700 1 _ |a Rankovic, Marija
|0 P:(DE-2719)9001085
|b 1
|u dzne
700 1 _ |a Favretto, Filippo
|0 P:(DE-2719)2811237
|b 2
700 1 _ |a Ukmar-Godec, Tina
|0 P:(DE-2719)9000315
|b 3
700 1 _ |a Strohäker, Timo
|0 P:(DE-2719)2812850
|b 4
700 1 _ |a Becker, Stefan
|b 5
700 1 _ |a Zweckstetter, Markus
|0 P:(DE-2719)2810591
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|e Last author
773 _ _ |a 10.1002/pro.4025
|g Vol. 30, no. 7, p. 1326 - 1336
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|n 7
|p 1326 - 1336
|t Protein science
|v 30
|y 2021
|x 1469-896X
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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