Signaling pathways and posttranslational modifications of tau in Alzheimer’s disease: the humanization of yeast cells
Authors:Jürgen J. Heinisch1 and Roland Brandt2
1 Universität Osnabrück, Fachbereich Biologie/Chemie, AG Genetik, Barbarastr. 11, D-49076 Osnabrück, Germany.
2 Universität Osnabrück, Fachbereich Biologie/Chemie, AG Neurobiologie, Barbarastr. 11, D-49076 Osnabrück, Germany.
Keywords:
Saccharomyces cerevisiae, Kluyveromyces lactis, gene expression, neurodegeneration, tauopathies, signal transduction.
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Conflict of interest statement:
The authors declare no conflict of interest.
Please cite this article as:
Jürgen J. Heinisch and Roland Brandt (2016). Signaling pathways and posttranslational modifications of tau in Alzheimer's disease: the humanization of yeast cells. Microbial Cell 3(4): 135-146. doi: 10.15698/mic2016.04.489
© 2016 Heinisch and Brandt. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
In the past decade, yeast have been frequently employed to study the molecular mechanisms of human neurodegenerative diseases, generally by means of heterologous expression of genes encoding the relevant hallmark proteins. However, it has become evident that substantial posttranslational modifications of many of these proteins are required for the development and progression of potentially disease relevant changes. This is exemplified by the neuronal tau proteins, which are critically involved in a class of neurodegenerative diseases collectively called tauopathies and which includes Alzheimer’s disease (AD) as its most common representative. In the course of the disease, tau changes its phosphorylation state and becomes hyperphosphorylated, gets truncated by proteolytic cleavage, is subject to O-glycosylation, sumoylation, ubiquitinylation, acetylation and some other modifications. This poses the important question, which of these posttranslational modifications are naturally occurring in the yeast model or can be reconstituted by heterologous gene expression. Here, we present an overview on common modifications as they occur in tau during AD, summarize their potential relevance with respect to disease mechanisms and refer to the native yeast enzyme orthologs capable to perform these modifications. We will also discuss potential approaches to humanize yeast in order to create modification patterns resembling the situation in mammalian cells, which could enhance the value of Saccharomyces cerevisiae and Kluyveromyces lactis as disease models.
doi: 10.15698/mic2016.04.489
Volume 3, pp. 135 to 146, published 27/03/2016.