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000280247 1001_ $$0P:(DE-2719)2812812$$aHochmair, Janine$$b0$$eFirst author$$udzne
000280247 245__ $$aStoichiometric 14-3-3ζ binding promotes phospho-Tau microtubule dissociation and reduces aggregation and condensation.
000280247 260__ $$aLondon$$bSpringer Nature$$c2025
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000280247 520__ $$aThe 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.
000280247 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0
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000280247 650_7 $$2NLM Chemicals$$a14-3-3 Proteins
000280247 650_7 $$2NLM Chemicals$$atau Proteins
000280247 650_7 $$2NLM Chemicals$$aProtein Aggregates
000280247 650_7 $$2NLM Chemicals$$aMAPT protein, human
000280247 650_2 $$2MeSH$$a14-3-3 Proteins: metabolism
000280247 650_2 $$2MeSH$$atau Proteins: metabolism
000280247 650_2 $$2MeSH$$atau Proteins: chemistry
000280247 650_2 $$2MeSH$$aMicrotubules: metabolism
000280247 650_2 $$2MeSH$$aHumans
000280247 650_2 $$2MeSH$$aPhosphorylation
000280247 650_2 $$2MeSH$$aProtein Binding
000280247 650_2 $$2MeSH$$aProtein Aggregates
000280247 650_2 $$2MeSH$$aProtein Aggregation, Pathological: metabolism
000280247 7001_ $$avan den Oetelaar, Maxime C M$$b1
000280247 7001_ $$0P:(DE-2719)9001996$$aRavatt, Leandre$$b2$$udzne
000280247 7001_ $$0P:(DE-2719)2812826$$aDiez, Lisa$$b3
000280247 7001_ $$aLemmens, Lenne J M$$b4
000280247 7001_ $$00000-0001-9000-4563$$aPonce-Lina, Renata$$b5
000280247 7001_ $$0P:(DE-2719)9002552$$aSankar, Rithika$$b6$$udzne
000280247 7001_ $$0P:(DE-2719)9000550$$aFranck, Maximilian$$b7$$udzne
000280247 7001_ $$0P:(DE-2719)9003541$$aNolte, Gesa$$b8$$udzne
000280247 7001_ $$0P:(DE-2719)9002208$$aSemenova, Ekaterina$$b9$$udzne
000280247 7001_ $$0P:(DE-2719)9001599$$aMohapatra, Satabdee$$b10$$udzne
000280247 7001_ $$00000-0001-7315-0315$$aOttmann, Christian$$b11
000280247 7001_ $$00000-0001-5675-511X$$aBrunsveld, Luc$$b12
000280247 7001_ $$0P:(DE-2719)2812695$$aWegmann, Susanne$$b13$$eLast author
000280247 773__ $$0PERI:(DE-600)2919698-X$$a10.1038/s42003-025-08548-0$$gVol. 8, no. 1, p. 1139$$n1$$p1139$$tCommunications biology$$v8$$x2399-3642$$y2025
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