Tau liquid-liquid phase separation in neurodegenerative diseases

被引:120
作者
Boyko, Solomiia [1 ]
Surewicz, Witold K. [1 ]
机构
[1] Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA
基金
美国国家卫生研究院;
关键词
PROTEIN; AGGREGATION; TRANSITIONS; MUTATIONS; DROPLETS; MATURATION; FILAMENTS;
D O I
10.1016/j.tcb.2022.01.011
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Aggregation of the microtubule-associated protein tau plays a major role in Alzheimer's disease and several other neurodegenerative disorders. An exciting recent development is the finding that, akin to some other proteins associated with neurodegenerative disease, tau has a high propensity to condensate via the mechanism of liquid-liquid phase separation (LLPS). Here, we discuss the evidence for tau LLPS in vitro, the molecular mechanisms of this reaction, and the role of post-translational modifications and pathogenic mutations in tau phase separation. We also discuss recent studies on tau LLPS in cells and the insights these studies provide regarding the link between LLPS and neurodegeneration in tauopathies.
引用
收藏
页码:611 / 623
页数:13
相关论文
共 89 条
[81]   Tau in physiology and pathology [J].
Wang, Yipeng ;
Mandelkow, Eckhard .
NATURE REVIEWS NEUROSCIENCE, 2016, 17 (01) :5-21
[82]   A current view on Tau protein phosphorylation in Alzheimer's disease [J].
Wegmann, Susanne ;
Biernat, Jacek ;
Mandelkow, Eckhard .
CURRENT OPINION IN NEUROBIOLOGY, 2021, 69 :131-138
[83]   Tau protein liquid-liquid phase separation can initiate tau aggregation [J].
Wegmann, Susanne ;
Eftekharzadeh, Bahareh ;
Tepper, Katharina ;
Zoltowska, Katarzyna M. ;
Bennett, Rachel E. ;
Dujardin, Simon ;
Laskowski, Pawel R. ;
MacKenzie, Danny ;
Kamath, Tarun ;
Commins, Caitlin ;
Vanderburg, Charles ;
Roe, Allyson D. ;
Fan, Zhanyun ;
Molliex, Amandine M. ;
Hernandez-Vega, Amayra ;
Muller, Daniel ;
Hyman, Anthony A. ;
Mandelkow, Eckhard ;
Taylor, J. Paul ;
Hyman, Bradley T. .
EMBO JOURNAL, 2018, 37 (07)
[84]   Stress granules and neurodegeneration [J].
Wolozin, Benjamin ;
Ivanov, Pavel .
NATURE REVIEWS NEUROSCIENCE, 2019, 20 (11) :649-666
[85]   Tau N-Terminal Inserts Regulate Tau Liquid-Liquid Phase Separation and Condensates Maturation in a Neuronal Cell Model [J].
Wu, Chengchen ;
Zhao, Junyi ;
Wu, Qiuping ;
Tan, Qiulong ;
Liu, Qiong ;
Xiao, Shifeng .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2021, 22 (18)
[86]   The LC Domain of hnRNPA2 Adopts Similar Conformations in Hydrogel Polymers, Liquid-like Droplets, and Nuclei [J].
Xiang, Siheng ;
Kato, Masato ;
Wu, Leeju C. ;
Lin, Yi ;
Ding, Ming ;
Zhang, Yajie ;
Yu, Yonghao ;
McKnight, Steven L. .
CELL, 2015, 163 (04) :829-839
[87]   Phase Separation and Neurodegenerative Diseases: A Disturbance in the Force [J].
Zbinden, Aurelie ;
Perez-Berlanga, Manuela ;
De Rossi, Pierre ;
Polymenidou, Magdalini .
DEVELOPMENTAL CELL, 2020, 55 (01) :45-68
[88]   The proline-rich domain promotes Tau liquid-liquid phase separation in cells [J].
Zhang, Xuemei ;
Vigers, Michael ;
McCarty, James ;
Rauch, Jennifer N. ;
Fredrickson, Glenn H. ;
Wilson, Maxwell Z. ;
Shea, Joan-Emma ;
Han, Songi ;
Kosik, Kenneth S. .
JOURNAL OF CELL BIOLOGY, 2020, 219 (11)
[89]   RNA stores tau reversibly in complex coacervates [J].
Zhang, Xuemei ;
Lin, Yanxian ;
Eschmann, Neil A. ;
Zhou, Hongjun ;
Rauch, Jennifer N. ;
Hernandez, Israel ;
Guzman, Elmer ;
Kosik, Kenneth S. ;
Han, Songi .
PLOS BIOLOGY, 2017, 15 (07)