Interplay between tau and α‐synuclein liquid–liquid phase separation

• DOI: 10.1002/pro.4025
• Publication Date: 2021-01-16T03:16:55Z
• Authors: Anna Siegert; Marija Rankovic; Filippo Favretto; Tina Ukmar‐Godec; Timo Strohäker; Stefan Becker; Markus Zweckstetter
• Keywords: Liquid liquid; Liquid phase

Abstract In Parkinson's disease with dementia, up to 50% of patients develop a high number tau‐containing neurofibrillary tangles. Tau‐based pathologies may thus act synergistically the α‐synuclein pathology confer worse prognosis. A better understanding relationship between two distinct is therefore required. Liquid–liquid phase separation (LLPS) proteins has recently been shown be important for protein aggregation involved in amyotrophic lateral sclerosis, whereas tau linked Alzheimer's disease. We investigated interaction and its consequences on LLPS. find have low propensity both, self‐coacervation RNA‐mediated LLPS at pH 7.4. However, full‐length but not carboxy‐terminally truncated efficiently partitions into tau/RNA droplets. further demonstrate that Cdk2‐phosphorylation promotes concentration RNA‐induced droplets, same time decreases amount inside NMR spectroscopy reveals carboxy‐terminal domain proline‐rich region P2 required recruitment The combined data suggest tau‐associated condensates can contribute synergistic aSyn/tau pathologies.