一种E3连接酶和自噬适配体通过嵌套相分离调节tau蛋白稳态

IF 17.3 1区生物学 Q1 CELL BIOLOGY Nature Cell Biology Pub Date : 2024-07-19 DOI:10.1038/s41556-024-01466-z

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引用次数: 0

摘要

编码 E3 泛素连接酶 TRIAD3A 的基因突变会导致成人发病型神经退行性疾病。我们发现，TRIAD3A 的泛素连接酶活性可促进其液-液相分离。TRIAD3A 与 tau 共同分离成液滴，tau 在液滴中形成纤维状聚集体。TRIAD3A通过其作为自噬适配体的作用介导这些聚集体的降解。

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An E3 ligase and autophagy adaptor regulates tau proteostasis through nested phase separation

Mutations in the gene encoding the E3 ubiquitin ligase TRIAD3A cause adult-onset neurodegenerative disorders. We reveal that the ubiquitin ligase activity of TRIAD3A promotes its liquid–liquid phase separation. TRIAD3A co-partitions with tau into droplets, where tau forms fibrillar aggregates. TRIAD3A mediates the degradation of these aggregates through its role as an autophagy adaptor.

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来源期刊

Nature Cell Biology 生物-细胞生物学

CiteScore

28.40

自引率

0.90%

发文量

219

审稿时长

3 months

期刊介绍： Nature Cell Biology, a prestigious journal, upholds a commitment to publishing papers of the highest quality across all areas of cell biology, with a particular focus on elucidating mechanisms underlying fundamental cell biological processes. The journal's broad scope encompasses various areas of interest, including but not limited to: -Autophagy -Cancer biology -Cell adhesion and migration -Cell cycle and growth -Cell death -Chromatin and epigenetics -Cytoskeletal dynamics -Developmental biology -DNA replication and repair -Mechanisms of human disease -Mechanobiology -Membrane traffic and dynamics -Metabolism -Nuclear organization and dynamics -Organelle biology -Proteolysis and quality control -RNA biology -Signal transduction -Stem cell biology

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