渗漏内体促使 tau 超过种子极限。
Leaky endosomes push tau over the seed limit.
机构信息
Department of Biology, University of York, York YO10 5DD, United Kingdom.
Department of Biology, University of York, York YO10 5DD, United Kingdom
出版信息
J Biol Chem. 2019 Dec 13;294(50):18967-18968. doi: 10.1074/jbc.H119.011687.
Abstract
The inter- and intracellular propagation of aggregated proteins like tau is emerging as a central mechanism behind progression of various neurodegenerative diseases. The steps by which tau aggregates and propagates is currently unclear. Chen now combine a cell-based model of tau aggregation with a CRISPR interference (CRISPRi) genetic screen to identify components of the endosomal sorting complex required for transport (ESCRT) machinery as mediators of intracellular propagation of tau aggregates. These findings reveal a role for endolysosomal integrity in blocking tau propagation.
摘要
聚集的蛋白质（如 tau）在细胞内外的传播，正成为各种神经退行性疾病进展的核心机制。tau 聚集和传播的步骤目前尚不清楚。Chen 现在将 tau 聚集的基于细胞的模型与 CRISPR 干扰（CRISPRi）遗传筛选相结合，以鉴定内体分选复合物必需的运输成分（ESCRT）机械作为 tau 聚集的细胞内传播的介质。这些发现揭示了内溶酶体完整性在阻止 tau 传播中的作用。
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