Journal Article

DZNE-2020-02414

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png TDP-43-mediated neuron loss in vivo requires RNA-binding activity.

Voigt, A. ; Herholz, D. ; Fiesel, F. C.DZNE* ; Kaur, K. ; Müller, D. ; Karsten, P. ; Weber, S. S.DZNE* ; Kahle, P.DZNE* ; Marquardt, T. ; Schulz, J. B. (Corresponding author)

2010
PLOS San Francisco, California, US

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Please use a persistent id in citations: doi:10.1371/journal.pone.0012247

Abstract: Alteration and/or mutations of the ribonucleoprotein TDP-43 have been firmly linked to human neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). The relative impacts of TDP-43 alteration, mutation, or inherent protein function on neural integrity, however, remain less clear--a situation confounded by conflicting reports based on transient and/or random-insertion transgenic expression. We therefore performed a stringent comparative investigation of impacts of these TDP-43 modifications on neural integrity in vivo. To achieve this, we systematically screened ALS/FTLD-associated and synthetic TDP-43 isoforms via same-site gene insertion and neural expression in Drosophila; followed by transposon-based motor neuron-specific transgenesis in a chick vertebrate system. Using this bi-systemic approach we uncovered a requirement of inherent TDP-43 RNA-binding function--but not ALS/FTLD-linked mutation, mislocalization, or truncation--for TDP-43-mediated neurotoxicity in vivo.

Keyword(s): Amyotrophic Lateral Sclerosis: genetics (MeSH) ; Animals (MeSH) ; Cell Line (MeSH) ; Chickens: genetics (MeSH) ; Chickens: metabolism (MeSH) ; Chickens: physiology (MeSH) ; DNA-Binding Proteins: genetics (MeSH) ; DNA-Binding Proteins: metabolism (MeSH) ; Drosophila melanogaster: cytology (MeSH) ; Drosophila melanogaster: genetics (MeSH) ; Drosophila melanogaster: metabolism (MeSH) ; Drosophila melanogaster: physiology (MeSH) ; Frontotemporal Lobar Degeneration: genetics (MeSH) ; Gene Expression Regulation (MeSH) ; Humans (MeSH) ; Intracellular Space: metabolism (MeSH) ; Locomotion (MeSH) ; Longevity (MeSH) ; Male (MeSH) ; Motor Neurons: metabolism (MeSH) ; Mutation (MeSH) ; Neurons: cytology (MeSH) ; Neurons: metabolism (MeSH) ; Organ Specificity (MeSH) ; Protein Binding (MeSH) ; Protein Transport (MeSH) ; RNA: metabolism (MeSH) ; DNA-Binding Proteins ; RNA

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Contributing Institute(s):

1. Regulatory RNA-protein interaction in neurodegenerative diseases (AG Krauß)
2. Functional Neurogenetics (AG Kahle 2)
3. Tübingen Pre 2020 (Tübingen Pre 2020)

Research Program(s):

1. 345 - Population Studies and Genetics (POF3-345) (POF3-345)
2. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2010

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