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001     274063
005     20260212170313.0
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|a 10.1073/pnas.2414176121
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|a pmid:39693350
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|a 0027-8424
024 7 _ |2 ISSN
|a 1091-6490
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037 _ _ |a DZNE-2025-00044
041 _ _ |a English
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100 1 _ |0 P:(DE-2719)2812532
|a Chakraborty, Pijush
|b 0
|u dzne
245 _ _ |a GSK3β phosphorylation catalyzes the aggregation of tau into Alzheimer's disease-like filaments.
260 _ _ |a Washington, DC
|b National Acad. of Sciences
|c 2024
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520 _ _ |a The pathological deposition of proteins is a hallmark of several devastating neurodegenerative diseases. These pathological deposits comprise aggregates of proteins that adopt distinct structures named strains. However, the molecular factors responsible for the formation of distinct aggregate strains are unknown. Here, we show that the serine/threonine kinase GSK3β catalyzes the aggregation of the protein tau into Alzheimer's disease (AD)-like filaments. We demonstrate that phosphorylation by GSK3β, but not by several other kinases, promotes the aggregation of full-length tau as well as enhances phase separation into gel-like condensate structures. Cryoelectron microscopy further reveals that the fibrils formed by GSK3β-phosphorylated tau adopt a fold comparable to that of paired helical filaments isolated from the brains of AD patients. Our results elucidate the intricate relationship between posttranslational modification and the formation of tau strains in neurodegenerative diseases.
536 _ _ |0 G:(DE-HGF)POF4-352
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650 _ 7 |2 Other
|a Alzheimer's disease
650 _ 7 |2 Other
|a NMR
650 _ 7 |2 Other
|a cryo-EM
650 _ 7 |2 Other
|a phosphorylation
650 _ 7 |2 Other
|a tau
650 _ 7 |2 NLM Chemicals
|a tau Proteins
650 _ 7 |0 EC 2.7.11.1
|2 NLM Chemicals
|a Glycogen Synthase Kinase 3 beta
650 _ 7 |2 NLM Chemicals
|a MAPT protein, human
650 _ 7 |2 NLM Chemicals
|a Protein Aggregates
650 _ 7 |0 EC 2.7.11.1
|2 NLM Chemicals
|a GSK3B protein, human
650 _ 2 |2 MeSH
|a tau Proteins: metabolism
650 _ 2 |2 MeSH
|a Alzheimer Disease: metabolism
650 _ 2 |2 MeSH
|a Alzheimer Disease: pathology
650 _ 2 |2 MeSH
|a Phosphorylation
650 _ 2 |2 MeSH
|a Humans
650 _ 2 |2 MeSH
|a Glycogen Synthase Kinase 3 beta: metabolism
650 _ 2 |2 MeSH
|a Protein Aggregation, Pathological: metabolism
650 _ 2 |2 MeSH
|a Protein Processing, Post-Translational
650 _ 2 |2 MeSH
|a Brain: metabolism
650 _ 2 |2 MeSH
|a Brain: pathology
650 _ 2 |2 MeSH
|a Cryoelectron Microscopy
650 _ 2 |2 MeSH
|a Protein Aggregates
700 1 _ |0 P:(DE-2719)2812657
|a Ibáñez de Opakua, Alain
|b 1
700 1 _ |0 P:(DE-2719)9001594
|a Purslow, Jeffrey
|b 2
|u dzne
700 1 _ |0 0000-0002-2094-1911
|a Fromm, Simon A
|b 3
700 1 _ |0 P:(DE-2719)9002139
|a Chatterjee, Debdeep
|b 4
700 1 _ |0 P:(DE-2719)9001567
|a Zachrdla, Milan
|b 5
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700 1 _ |0 P:(DE-2719)9002416
|a Zhuang, Shannon
|b 6
700 1 _ |0 0009-0003-1991-3977
|a Puri, Sambhavi
|b 7
700 1 _ |0 0000-0003-2068-1475
|a Wolozin, Benjamin
|b 8
700 1 _ |0 P:(DE-2719)2810591
|a Zweckstetter, Markus
|b 9
|e Last author
773 _ _ |0 PERI:(DE-600)1461794-8
|a 10.1073/pnas.2414176121
|g Vol. 121, no. 52, p. e2414176121
|n 52
|p e2414176121
|t Proceedings of the National Academy of Sciences of the United States of America
|v 121
|x 0027-8424
|y 2024
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