Tau N-Terminal Inserts Regulate Tau Liquid-Liquid Phase Separation and Condensates Maturation in a Neuronal Cell Model
| Autor: | Qiong Liu, Junyi Zhao, Qiulong Tan, Qiuping Wu, Shifeng Xiao, Chengchen Wu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
liquid–liquid phase separation
QH301-705.5 Liquid-Liquid Extraction Tau protein Fluorescent Antibody Technique tau Proteins Protein aggregation Protein Aggregation Pathological Article Catalysis Cell Line protein aggregation tau isoforms Inorganic Chemistry Protein Aggregates mental disorders medicine Humans Protein Isoforms Liquid liquid Biology (General) Physical and Theoretical Chemistry QD1-999 Molecular Biology Spectroscopy Neurons biology Chemistry Organic Chemistry Colocalization General Medicine Human brain Computer Science Applications Tau isoforms medicine.anatomical_structure Cell culture Cytoplasm Biophysics biology.protein p62 protein Biomarkers Protein Binding |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 9728, p 9728 (2021) International Journal of Molecular Sciences Volume 22 Issue 18 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22189728 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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