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000136092 0247_ $$2doi$$a10.1371/journal.pone.0012247
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000136092 1001_ $$0P:(DE-HGF)0$$aVoigt, Aaron$$b0
000136092 245__ $$aTDP-43-mediated neuron loss in vivo requires RNA-binding activity.
000136092 260__ $$aSan Francisco, California, US$$bPLOS$$c2010
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000136092 520__ $$aAlteration 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.
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000136092 650_7 $$2NLM Chemicals$$aDNA-Binding Proteins
000136092 650_7 $$063231-63-0$$2NLM Chemicals$$aRNA
000136092 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: genetics
000136092 650_2 $$2MeSH$$aAnimals
000136092 650_2 $$2MeSH$$aCell Line
000136092 650_2 $$2MeSH$$aChickens: genetics
000136092 650_2 $$2MeSH$$aChickens: metabolism
000136092 650_2 $$2MeSH$$aChickens: physiology
000136092 650_2 $$2MeSH$$aDNA-Binding Proteins: genetics
000136092 650_2 $$2MeSH$$aDNA-Binding Proteins: metabolism
000136092 650_2 $$2MeSH$$aDrosophila melanogaster: cytology
000136092 650_2 $$2MeSH$$aDrosophila melanogaster: genetics
000136092 650_2 $$2MeSH$$aDrosophila melanogaster: metabolism
000136092 650_2 $$2MeSH$$aDrosophila melanogaster: physiology
000136092 650_2 $$2MeSH$$aFrontotemporal Lobar Degeneration: genetics
000136092 650_2 $$2MeSH$$aGene Expression Regulation
000136092 650_2 $$2MeSH$$aHumans
000136092 650_2 $$2MeSH$$aIntracellular Space: metabolism
000136092 650_2 $$2MeSH$$aLocomotion
000136092 650_2 $$2MeSH$$aLongevity
000136092 650_2 $$2MeSH$$aMale
000136092 650_2 $$2MeSH$$aMotor Neurons: metabolism
000136092 650_2 $$2MeSH$$aMutation
000136092 650_2 $$2MeSH$$aNeurons: cytology
000136092 650_2 $$2MeSH$$aNeurons: metabolism
000136092 650_2 $$2MeSH$$aOrgan Specificity
000136092 650_2 $$2MeSH$$aProtein Binding
000136092 650_2 $$2MeSH$$aProtein Transport
000136092 650_2 $$2MeSH$$aRNA: metabolism
000136092 7001_ $$0P:(DE-HGF)0$$aHerholz, David$$b1
000136092 7001_ $$0P:(DE-2719)9000399$$aFiesel, Fabienne C$$b2$$udzne
000136092 7001_ $$0P:(DE-HGF)0$$aKaur, Kavita$$b3
000136092 7001_ $$0P:(DE-HGF)0$$aMüller, Daniel$$b4
000136092 7001_ $$0P:(DE-HGF)0$$aKarsten, Peter$$b5
000136092 7001_ $$0P:(DE-2719)2662310$$aWeber, Stephanie S$$b6
000136092 7001_ $$0P:(DE-2719)2810803$$aKahle, Phillip$$b7
000136092 7001_ $$0P:(DE-HGF)0$$aMarquardt, Till$$b8
000136092 7001_ $$0P:(DE-HGF)0$$aSchulz, Jörg B$$b9$$eCorresponding author
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