TDP-43-mediated neuron loss In Vivo requires RNA-binding activity

Aaron Voigt, David Herholz, Fabienne Fiesel, Kavita Kaur, Daniel Müller, Peter Karsten, Stephanie S. Weber, Philipp J. Kahle, Till Marquardt, Jörg B. Schulz

Research output: Contribution to journalArticle

114 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere12247
JournalPloS one
Volume5
Issue number8
DOIs
StatePublished - Oct 20 2010
Externally publishedYes

Fingerprint

Frontotemporal Lobar Degeneration
Amyotrophic Lateral Sclerosis
Neurons
neurons
RNA
Neurodegenerative diseases
mutation
Mutation
Ribonucleoproteins
ribonucleoproteins
Gene Transfer Techniques
Protein Isoforms
neurotoxicity
Genes
Insertional Mutagenesis
neurodegenerative diseases
Motor Neurons
motor neurons
Neurodegenerative Diseases
transposons

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Voigt, A., Herholz, D., Fiesel, F., Kaur, K., Müller, D., Karsten, P., ... Schulz, J. B. (2010). TDP-43-mediated neuron loss In Vivo requires RNA-binding activity. PloS one, 5(8), [e12247]. https://doi.org/10.1371/journal.pone.0012247

TDP-43-mediated neuron loss In Vivo requires RNA-binding activity. / Voigt, Aaron; Herholz, David; Fiesel, Fabienne; Kaur, Kavita; Müller, Daniel; Karsten, Peter; Weber, Stephanie S.; Kahle, Philipp J.; Marquardt, Till; Schulz, Jörg B.

In: PloS one, Vol. 5, No. 8, e12247, 20.10.2010.

Research output: Contribution to journalArticle

Voigt, A, Herholz, D, Fiesel, F, Kaur, K, Müller, D, Karsten, P, Weber, SS, Kahle, PJ, Marquardt, T & Schulz, JB 2010, 'TDP-43-mediated neuron loss In Vivo requires RNA-binding activity', PloS one, vol. 5, no. 8, e12247. https://doi.org/10.1371/journal.pone.0012247
Voigt A, Herholz D, Fiesel F, Kaur K, Müller D, Karsten P et al. TDP-43-mediated neuron loss In Vivo requires RNA-binding activity. PloS one. 2010 Oct 20;5(8). e12247. https://doi.org/10.1371/journal.pone.0012247
Voigt, Aaron ; Herholz, David ; Fiesel, Fabienne ; Kaur, Kavita ; Müller, Daniel ; Karsten, Peter ; Weber, Stephanie S. ; Kahle, Philipp J. ; Marquardt, Till ; Schulz, Jörg B. / TDP-43-mediated neuron loss In Vivo requires RNA-binding activity. In: PloS one. 2010 ; Vol. 5, No. 8.
@article{b52e619a6aa44d61853edc10ef1edf7c,
title = "TDP-43-mediated neuron loss In Vivo requires RNA-binding activity",
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.",
author = "Aaron Voigt and David Herholz and Fabienne Fiesel and Kavita Kaur and Daniel M{\"u}ller and Peter Karsten and Weber, {Stephanie S.} and Kahle, {Philipp J.} and Till Marquardt and Schulz, {J{\"o}rg B.}",
year = "2010",
month = "10",
day = "20",
doi = "10.1371/journal.pone.0012247",
language = "English (US)",
volume = "5",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "8",

}

TY - JOUR

T1 - TDP-43-mediated neuron loss In Vivo requires RNA-binding activity

AU - Voigt, Aaron

AU - Herholz, David

AU - Fiesel, Fabienne

AU - Kaur, Kavita

AU - Müller, Daniel

AU - Karsten, Peter

AU - Weber, Stephanie S.

AU - Kahle, Philipp J.

AU - Marquardt, Till

AU - Schulz, Jörg B.

PY - 2010/10/20

Y1 - 2010/10/20

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77957918535&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957918535&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0012247

DO - 10.1371/journal.pone.0012247

M3 - Article

VL - 5

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 8

M1 - e12247

ER -