Universität zu Köln

Gorsky, Marianna Karina, Burnouf, Sylvie, Dols, Jacqueline, Mandelkow, Eckhard and Partridge, Linda ORCID: 0000-0001-9615-0094 (2016). Acetylation mimic of lysine 280 exacerbates human Tau neurotoxicity in vivo. Sci Rep, 6. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

Dysfunction and accumulation of the microtubule-associated human Tau (hTau) protein into intraneuronal aggregates is observed in many neurodegenerative disorders including Alzheimer's disease (AD). Reversible lysine acetylation has recently emerged as a post-translational modification that may play an important role in the modulation of hTau pathology. Acetylated hTau species have been observed within hTau aggregates in human AD brains and multi-acetylation of hTau in vitro regulates its propensity to aggregate. However, whether lysine acetylation at position 280 (K280) modulates hTau-induced toxicity in vivo is unknown. We generated new Drosophila transgenic models of hTau pathology to evaluate the contribution of K280 acetylation to hTau toxicity, by analysing the respective toxicity of pseudo-acetylated (K280Q) and pseudo-de-acetylated (K280R) mutant forms of hTau. We observed that mis-expression of pseudo-acetylated K280Q-hTau in the adult fly nervous system potently exacerbated fly locomotion defects and photoreceptor neurodegeneration. In addition, modulation of K280 influenced total hTau levels and phosphorylation without changing hTau solubility. Altogether, our results indicate that pseudo-acetylation of the single K280 residue is sufficient to exacerbate hTau neurotoxicity in vivo, suggesting that acetylated K280-hTau species contribute to the pathological events leading to neurodegeneration in AD.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gorsky, Marianna Karina UNSPECIFIED UNSPECIFIED UNSPECIFIED Burnouf, Sylvie UNSPECIFIED UNSPECIFIED UNSPECIFIED Dols, Jacqueline UNSPECIFIED UNSPECIFIED UNSPECIFIED Mandelkow, Eckhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Partridge, Linda UNSPECIFIED orcid.org/0000-0001-9615-0094 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-281717
DOI:	10.1038/srep22685
Journal or Publication Title:	Sci Rep
Volume:	6
Date:	2016
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ALZHEIMERS-DISEASE; AGGREGATION; DROSOPHILA; PROTEIN; TAUOPATHY; NEURODEGENERATION; MODEL; PHOSPHORYLATION; PROPAGATION; INHIBITION Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28171