Universität zu Köln

Gorsky, Marianna Karina, Burnouf, Sylvie, Sofola-Adesakin, Oyinkan, Dols, Jacqueline, Augustin, Hrvoje, Weigelt, Carina Marianne ORCID: 0000-0001-8556-4259, Groenke, Sebastian and Partridge, Linda ORCID: 0000-0001-9615-0094 (2017). Pseudo-acetylation of multiple sites on human Tau proteins alters Tau phosphorylation and microtubule binding, and ameliorates amyloid beta toxicity. Sci Rep, 7. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

Tau is a microtubule-associated protein that is highly soluble and natively unfolded. Its dysfunction is involved in the pathogenesis of several neurodegenerative disorders including Alzheimer's disease (AD), where it aggregates within neurons. Deciphering the physiological and pathogenic roles of human Tau (hTau) is crucial to further understand the mechanisms leading to its dysfunction in vivo. We have used a knock-out/knock-in strategy in Drosophila to generate a strain with hTau inserted into the endogenous fly tau locus and expressed under the control of the endogenous fly tau promoter, thus avoiding potential toxicity due to genetic over-expression. hTau knock-in (KI) proteins were expressed at normal, endogenous levels, bound to fly microtubules and were post-translationally modified, hence displaying physiological properties. We used this new model to investigate the effects of acetylation on hTau toxicity in vivo. The simultaneous pseudo-acetylation of hTau at lysines 163, 280, 281 and 369 drastically decreased hTau phosphorylation and significantly reduced its binding to microtubules in vivo. These molecular alterations were associated with ameliorated amyloid beta toxicity. Our results indicate acetylation of hTau on multiple sites regulates its biology and ameliorates amyloid beta toxicity in vivo.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gorsky, Marianna Karina UNSPECIFIED UNSPECIFIED UNSPECIFIED Burnouf, Sylvie UNSPECIFIED UNSPECIFIED UNSPECIFIED Sofola-Adesakin, Oyinkan UNSPECIFIED UNSPECIFIED UNSPECIFIED Dols, Jacqueline UNSPECIFIED UNSPECIFIED UNSPECIFIED Augustin, Hrvoje UNSPECIFIED UNSPECIFIED UNSPECIFIED Weigelt, Carina Marianne UNSPECIFIED orcid.org/0000-0001-8556-4259 UNSPECIFIED Groenke, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Partridge, Linda UNSPECIFIED orcid.org/0000-0001-9615-0094 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-221375
DOI:	10.1038/s41598-017-10225-0
Journal or Publication Title:	Sci Rep
Volume:	7
Date:	2017
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language IN-VIVO; DROSOPHILA; TAUOPATHIES; NEURODEGENERATION; AGGREGATION; KINASES; DISEASE Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22137