期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 18, 页码 -出版社
MDPI
DOI: 10.3390/ijms22189728
关键词
liquid-liquid phase separation; tau isoforms; protein aggregation; p62 protein
资金
- Shenzhen Science and Technology Innovation Commission [JCYJ20180507182417779]
- Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions [2021SHIBS0003]
The study shows that tau protein can undergo LLPS in neurons, forming different types of condensates in cells based on the N-terminal inserts of tau isoforms. The absence of N-terminal inserts significantly affects the size and functionality of tau condensates.
The microtubule-associated protein tau can undergo liquid-liquid phase separation (LLPS) to form membraneless condensates in neurons, yet the underlying molecular mechanisms and functions of tau LLPS and tau droplets remain to be elucidated. The human brain contains mainly 6 tau isoforms with different numbers of microtubule-binding repeats (3R, 4R) and N-terminal inserts (0N, 1N, 2N). However, little is known about the role of N-terminal inserts. Here we observed the dynamics of three tau isoforms with different N-terminal inserts in live neuronal cell line HT22. We validated tau LLPS in cytoplasm and found that 2N-tau forms liquid-like, hollow-shell droplets. Tau condensates became smaller in 1N-tau comparing with 2N-tau, while no obvious tau accumulated dots were shown in 0N-tau. The absence of N-terminal inserts significantly affected condensate colocalization of tau and p62. The results reveal insights into the tau LLPS assembly mechanism and functional effects of N-terminal inserts in tau.
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