RNAi-Mediated Reverse Genetic Screen Identified Drosophila Chaperones Regulating Eye and Neuromuscular Junction Morphology

G3 : Genes - Genomes - Genetics
Sandeep RautVimlesh Kumar

Abstract

Accumulation of toxic proteins in neurons has been linked with the onset of neurodegenerative diseases, which in many cases are characterized by altered neuronal function and synapse loss. Molecular chaperones help protein folding and the resolubilization of unfolded proteins, thereby reducing the protein aggregation stress. While most of the chaperones are expressed in neurons, their functional relevance remains largely unknown. Here, using bioinformatics analysis, we identified 95 Drosophila chaperones and classified them into seven different classes. Ubiquitous actin5C-Gal4-mediated RNAi knockdown revealed that ∼50% of the chaperones are essential in Drosophila Knocking down these genes in eyes revealed that ∼30% of the essential chaperones are crucial for eye development. Using neuron-specific knockdown, immunocytochemistry, and robust behavioral assays, we identified a new set of chaperones that play critical roles in the regulation of Drosophila NMJ structural organization. Together, our data present the first classification and comprehensive analysis of Drosophila chaperones. Our screen identified a new set of chaperones that regulate eye and NMJ morphogenesis. The outcome of the screen reported here provides a useful re...Continue Reading

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Citations

Nov 8, 2018·International Journal of Molecular Sciences·Teresa JaglaKrzysztof Jagla
Mar 23, 2019·Frontiers in Genetics·Sarah C Hughes, Andrew J Simmonds

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Methods Mentioned

BETA
protein folding

Software Mentioned

BLAST
ImageJ
BLASTP
GraphPad
GraphPad Prism
Adobe Photoshop

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