CG6115, a novel gene involved in neurodegeneration in Drosophila melanogaster, is needed in muscle during development

BERNABO G, REZÁVAL C, AVENDAÑO LA, FRANCO DL, WERBAJH S, CERIANI MF

Quebec City

Congreso; 5th CAN Meeting; 2011

CAN

Drosophila melanogaster has orthologs of about 64% of all unique genes known to be involved in neurodegeneration in humans. To identify novel genes related to this process a misexpression screen has been carried out in our laboratory. It consisted in examining locomotor behavior in young and aged flies. Flies that showed a progressive loss of rhythmic activity could reveal novel genes involved in neurodegenerative mechanisms. One of the mutants, 100B, which, as a result of the P element insertion, shows a striking downregulation of CG6115 expression. CG6115 encodes a gene of unknown function. BLAST analysis of the putative protein encoded by this gene suggests that it belongs to the Complex 1 LYR protein superfamily. Proteins in this family have been identified as a component of the higher eukaryotic NADH complex. Homozygous 100B mutants cannot progress beyond second instar larvae and have an abnormal feeding behavior. To address CG6115 relevance in different tissues we employed different GAL4 lines to express an RNAi directed towards CG6115. Muscle related GAL4s were found to mimic homozygous mutant behavior in larvae. Interestingly, adult flies expressing the RNAi specific to CG6115 in pigment dispersor factor positive neurons (a key circuit in the control of rest-activity cycles), when screened in locomotor behavior, showed progressive arrythmicity and period lengthening. In addition, flies expressing CG6115 RNAi under the glass Multimer Reporter promoter show severe eye defects in approximately 23% of the individuals. Taken together these results we propose CG6115 could play a role in neurodegeneration.