Neuronal Function and Dysfunction of Drosophila dTDP

摘要: Background TDP-43 is an RNA- and DNA-binding protein well conserved in animals including the mammals, Drosophila, C. elegans. In multi-function TDP-43 encoded by TARDBP gene a signature of ubiquitin-positive inclusions (UBIs) diseased neuronal/glial cells range neurodegenerative diseases amyotrophic lateral sclerosis (ALS) frontotemporal lobar degeneration (FTLD-U). Methodology/Principal Findings We have studied function dysfunction Drosophila ortholog mammalian gene, dTDP, genetic, behavioral, molecular, cytological analyses. It was found that depletion dTDP expression caused locomotion defect accompanied with increase number boutons at neuromuscular junctions (NMJ). These phenotypes could be rescued overexpression motor neurons. contrast, neurons also resulted reduced larval adult locomotor activities, but this decrease axon branches NMJ. Significantly, constitutive mushroom bodies smaller axonal lobes as severe learning deficiency. On other hand, body-specific knockdown did not affect structure bodies, it impaired ability flies, albeit moderately. Overexpression led to formation cytosolic (+) aggregates. Conclusion/Significance These data together demonstrate neuronal functions implication TDP-43, locomotion. The effects mis-expression on NMJ suggest eukaryotic guards against over development synapses. conservation regulatory pathways dysfunctions shows feasibility using flies model system for studying normal proteinopathies vertebrates human.