000163787 001__ 163787
000163787 005__ 20240320115522.0
000163787 0247_ $$2pmc$$apmc:PMC9156969
000163787 0247_ $$2doi$$a10.15252/embj.2021108882
000163787 0247_ $$2ISSN$$a0261-4189
000163787 0247_ $$2ISSN$$a1460-2075
000163787 0247_ $$2altmetric$$aaltmetric:124834212
000163787 0247_ $$2pmid$$apmid:35298090
000163787 037__ $$aDZNE-2022-00525
000163787 082__ $$a570
000163787 1001_ $$0P:(DE-2719)2812812$$aHochmair, Janine$$b0$$eFirst author$$udzne
000163787 245__ $$aMolecular crowding and RNA synergize to promote phase separation, microtubule interaction, and seeding of Tau condensates
000163787 260__ $$aHoboken, NJ [u.a.]$$bWiley$$c2022
000163787 3367_ $$2DRIVER$$aarticle
000163787 3367_ $$2DataCite$$aOutput Types/Journal article
000163787 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1654785637_6363
000163787 3367_ $$2BibTeX$$aARTICLE
000163787 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000163787 3367_ $$00$$2EndNote$$aJournal Article
000163787 500__ $$a(CC BY-NC-ND)
000163787 520__ $$aBiomolecular condensation of the neuronal microtubule-associated protein Tau (MAPT) can be induced by coacervation with polyanions like RNA, or by molecular crowding. Tau condensates have been linked to both functional microtubule binding and pathological aggregation in neurodegenerative diseases. We find that molecular crowding and coacervation with RNA, two conditions likely coexisting in the cytosol, synergize to enable Tau condensation at physiological buffer conditions and to produce condensates with a strong affinity to charged surfaces. During condensate-mediated microtubule polymerization, their synergy enhances bundling and spatial arrangement of microtubules. We further show that different Tau condensates efficiently induce pathological Tau aggregates in cells, including accumulations at the nuclear envelope that correlate with nucleocytoplasmic transport deficits. Fluorescent lifetime imaging reveals different molecular packing densities of Tau in cellular accumulations and a condensate-like density for nuclear-envelope Tau. These findings suggest that a complex interplay between interaction partners, post-translational modifications, and molecular crowding regulates the formation and function of Tau condensates. Conditions leading to prolonged existence of Tau condensates may induce the formation of seeding-competent Tau and lead to distinct cellular Tau accumulations.
000163787 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0
000163787 588__ $$aDataset connected to CrossRef, Journals: pub.dzne.de
000163787 650_2 $$2MeSH$$aHumans
000163787 650_2 $$2MeSH$$aMicrotubules: metabolism
000163787 650_2 $$2MeSH$$aNeurodegenerative Diseases: metabolism
000163787 650_2 $$2MeSH$$aNeurons: metabolism
000163787 650_2 $$2MeSH$$aProtein Binding
000163787 650_2 $$2MeSH$$aRNA: metabolism
000163787 650_2 $$2MeSH$$atau Proteins: metabolism
000163787 7001_ $$00000-0001-9585-4743$$aExner, Christian$$b1
000163787 7001_ $$0P:(DE-2719)9000550$$aFranck, Maximilian$$b2$$udzne
000163787 7001_ $$0P:(DE-2719)9000533$$aDominguez-Baquero, Alvaro$$b3$$udzne
000163787 7001_ $$0P:(DE-2719)2812826$$aDiez, Lisa$$b4$$udzne
000163787 7001_ $$aBrognaro, Hévila$$b5
000163787 7001_ $$00000-0002-7359-0318$$aKraushar, Matthew L$$b6
000163787 7001_ $$aMielke, Thorsten$$b7
000163787 7001_ $$aRadbruch, Helena$$b8
000163787 7001_ $$0P:(DE-2719)2812350$$aKaniyappan, Senthilvelrajan$$b9$$udzne
000163787 7001_ $$00000-0003-3409-1791$$aFalke, Sven$$b10
000163787 7001_ $$0P:(DE-2719)2541671$$aMandelkow, Eckhard$$b11$$udzne
000163787 7001_ $$00000-0002-3879-5019$$aBetzel, Christian$$b12
000163787 7001_ $$0P:(DE-2719)2812695$$aWegmann, Susanne$$b13$$eLast author$$udzne
000163787 773__ $$0PERI:(DE-600)1467419-1$$a10.15252/embj.2021108882$$n11$$pe108882$$tThe EMBO journal$$v41$$x0261-4189$$y2022
000163787 8564_ $$uhttps://pub.dzne.de/record/163787/files/Molecular%20crowding%20and%20RNA%20synergize%20to%20promote%20phase%20separation%2C%20microtubule%20interaction%2C%20and%20seeding%20of%20Tau%20condensates.pdf$$yOpenAccess
000163787 8564_ $$uhttps://pub.dzne.de/record/163787/files/Molecular%20crowding%20and%20RNA%20synergize%20to%20promote%20phase%20separation%2C%20microtubule%20interaction%2C%20and%20seeding%20of%20Tau%20condensates.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000163787 909CO $$ooai:pub.dzne.de:163787$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire
000163787 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812812$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b0$$kDZNE
000163787 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9000550$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b2$$kDZNE
000163787 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9000533$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b3$$kDZNE
000163787 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812826$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b4$$kDZNE
000163787 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812350$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b9$$kDZNE
000163787 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2541671$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b11$$kDZNE
000163787 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812695$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b13$$kDZNE
000163787 9131_ $$0G:(DE-HGF)POF4-352$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vDisease Mechanisms$$x0
000163787 9141_ $$y2022
000163787 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2022-11-12
000163787 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2022-11-12
000163787 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2022-11-12
000163787 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2021-01-30
000163787 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2022-11-12
000163787 915__ $$0LIC:(DE-HGF)CCBYNCND4$$2HGFVOC$$aCreative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0
000163787 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bEMBO J : 2021$$d2022-11-12
000163787 915__ $$0StatID:(DE-HGF)9910$$2StatID$$aIF >= 10$$bEMBO J : 2021$$d2022-11-12
000163787 915__ $$0StatID:(DE-HGF)3001$$2StatID$$aDEAL Wiley$$d2021-01-30$$wger
000163787 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2021-01-30
000163787 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2022-11-12
000163787 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000163787 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2022-11-12
000163787 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2022-11-12
000163787 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2021-01-30
000163787 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2022-11-12
000163787 9201_ $$0I:(DE-2719)1810006$$kAG Wegmann$$lProtein Actions in Neurodegeneration$$x0
000163787 9201_ $$0I:(DE-2719)1013014$$kAG Mandelkow 1$$lStructural Principles of Neurodegeneration$$x1
000163787 9201_ $$0I:(DE-2719)1013015$$kAG Mandelkow 2$$lCell and Animal Models of Neurodegeneration$$x2
000163787 980__ $$ajournal
000163787 980__ $$aVDB
000163787 980__ $$aUNRESTRICTED
000163787 980__ $$aI:(DE-2719)1810006
000163787 980__ $$aI:(DE-2719)1013014
000163787 980__ $$aI:(DE-2719)1013015
000163787 9801_ $$aFullTexts