Home > Publications Database > Stoichiometric 14-3-3ζ binding promotes phospho-Tau microtubule dissociation and reduces aggregation and condensation. > print

001     280247
005     20250831001820.0
024 7 _ |a 10.1038/s42003-025-08548-0
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100 1 _ |a Hochmair, Janine
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245 _ _ |a Stoichiometric 14-3-3ζ binding promotes phospho-Tau microtubule dissociation and reduces aggregation and condensation.
260 _ _ |a London
|c 2025
|b Springer Nature
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520 _ _ |a The microtubule (MT) association of protein Tau is decreased upon phosphorylation. Increased levels of phosphorylated Tau in the cytosol pose the risk of pathological aggregation, as observed in neurodegenerative diseases. We show that binding of 14-3-3ζ enhances cytosolic Tau solubility by promoting phosphorylated Tau removal from MTs, while simultaneously inhibiting Tau aggregation both directly and indirectly via suppression of condensate formation. These 14-3-3ζ activities depend on site-specific binding of 14-3-3 to Tau phosphorylated at S214 and S324. At sub-stoichiometric 14-3-3ζ concentrations, or in the presence of other 14-3-3ζ binding partners, multivalent electrostatic interactions promote Tau:14-3-3ζ co-condensation, offering a phosphorylation-independent mode of Tau-14-3-3ζ interactions. Given the high abundance of 14-3-3 proteins in the brain, 14-3-3 binding could provide efficient multi-modal chaperoning activity for Tau in the healthy brain and be important for preventing Tau aggregation in disease.
536 _ _ |a 352 - Disease Mechanisms (POF4-352)
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650 _ 7 |a 14-3-3 Proteins
|2 NLM Chemicals
650 _ 7 |a tau Proteins
|2 NLM Chemicals
650 _ 7 |a Protein Aggregates
|2 NLM Chemicals
650 _ 7 |a MAPT protein, human
|2 NLM Chemicals
650 _ 2 |a 14-3-3 Proteins: metabolism
|2 MeSH
650 _ 2 |a tau Proteins: metabolism
|2 MeSH
650 _ 2 |a tau Proteins: chemistry
|2 MeSH
650 _ 2 |a Microtubules: metabolism
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Phosphorylation
|2 MeSH
650 _ 2 |a Protein Binding
|2 MeSH
650 _ 2 |a Protein Aggregates
|2 MeSH
650 _ 2 |a Protein Aggregation, Pathological: metabolism
|2 MeSH
700 1 _ |a van den Oetelaar, Maxime C M
|b 1
700 1 _ |a Ravatt, Leandre
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700 1 _ |a Diez, Lisa
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700 1 _ |a Lemmens, Lenne J M
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700 1 _ |a Ponce-Lina, Renata
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700 1 _ |a Sankar, Rithika
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700 1 _ |a Franck, Maximilian
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700 1 _ |a Nolte, Gesa
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700 1 _ |a Semenova, Ekaterina
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700 1 _ |a Mohapatra, Satabdee
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700 1 _ |a Ottmann, Christian
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700 1 _ |a Brunsveld, Luc
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700 1 _ |a Wegmann, Susanne
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773 _ _ |a 10.1038/s42003-025-08548-0
|g Vol. 8, no. 1, p. 1139
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|t Communications biology
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