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
[31]   Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases [J].
Guo, Jing L. ;
Lee, Virginia M. Y. .
NATURE MEDICINE, 2014, 20 (02) :130-138
[32]   Roles of tau protein in health and disease [J].
Guo, Tong ;
Noble, Wendy ;
Hanger, Diane P. .
ACTA NEUROPATHOLOGICA, 2017, 133 (05) :665-704
[33]   Local Nucleation of Microtubule Bundles through Tubulin Concentration into a Condensed Tau Phase [J].
Hernandez-Vega, Amayra ;
Braun, Marcus ;
Scharrel, Lara ;
Jahnel, Marcus ;
Wegmann, Susanne ;
Hyman, Bradley T. ;
Alberti, Simon ;
Diez, Stefan ;
Hyman, Anthony A. .
CELL REPORTS, 2017, 20 (10) :2304-2312
[34]   Tau gene mutations:: dissecting the pathogenesis of FTDP-17 [J].
Ingram, EM ;
Spillantini, MG .
TRENDS IN MOLECULAR MEDICINE, 2002, 8 (12) :555-562
[35]   Tau and neurodegenerative disease: the story so far [J].
Iqbal, Khalid ;
Liu, Fei ;
Gong, Cheng-Xin .
NATURE REVIEWS NEUROLOGY, 2016, 12 (01) :15-27
[36]   Cellular polyamines condense hyperphosphorylated Tau, triggering Alzheimer's disease [J].
Ivanov, Stefan M. ;
Atanasova, Mariyana ;
Dimitrov, Ivan ;
Doytchinova, Irini A. .
SCIENTIFIC REPORTS, 2020, 10 (01)
[37]   Protein condensates as aging Maxwell fluids [J].
Jawerth, Louise ;
Fischer-Friedrich, Elisabeth ;
Saha, Suropriya ;
Wang, Jie ;
Franzmann, Titus ;
Zhang, Xiaojie ;
Sachweh, Jenny ;
Ruer, Martine ;
Ijavi, Mandiye ;
Saha, Shambaditya ;
Mahamid, Julia ;
Hyman, Anthony A. ;
Juelicher, Frank .
SCIENCE, 2020, 370 (6522) :1317-+
[38]   Interaction of tau with HNRNPA2B1 and N6-methyladenosine RNA mediates the progression of tauopathy [J].
Jiang, Lulu ;
Lin, Weiwei ;
Zhang, Cheng ;
Ash, Peter E. A. ;
Verma, Mamta ;
Kwan, Julian ;
van Vliet, Emily ;
Yang, Zhuo ;
Cruz, Anna Lourdes ;
Boudeau, Samantha ;
Maziuk, Brandon F. ;
Lei, Shuwen ;
Song, Jaehyup ;
Alvarez, Victor E. ;
Hovde, Stacy ;
Abisambra, Jose F. ;
Kuo, Min-Hao ;
Kanaan, Nicholas ;
Murray, Melissa E. ;
Crary, John F. ;
Zhao, Jian ;
Cheng, Ji-Xin ;
Petrucelli, Leonard ;
Li, Hu ;
Emili, Andrew ;
Wolozin, Benjamin .
MOLECULAR CELL, 2021, 81 (20) :4209-+
[39]   Liquid-liquid phase separation induces pathogenic tau conformations in vitro [J].
Kanaan, Nicholas M. ;
Hamel, Chelsey ;
Grabinski, Tessa ;
Combs, Benjamin .
NATURE COMMUNICATIONS, 2020, 11 (01)
[40]   Pathologic tau conformer ensembles induce dynamic, liquid-liquid phase separation events at the nuclear envelope [J].
Kang, Sang-Gyun ;
Han, Zhuang Zhuang ;
Daude, Nathalie ;
McNamara, Emily ;
Wohlgemuth, Serene ;
Molina-Porcel, Laura ;
Safar, Jiri G. ;
Mok, Sue-Ann ;
Westaway, David .
BMC BIOLOGY, 2021, 19 (01)