Drosophila DFMR1 Interacts with Genes of the Lgl-Pathway in the Brain Synaptic Architecture

Abstract

ABSTRACTFragile X syndrome is a genetic neuro-developmental disorder, caused by the transcriptional inactivation of the gene Fmr1 (Fragile X mental retardation 1). The lack of its protein product (FMRP) is accompanied by defects in synaptic maturation and morphology and by synaptic dysfunction throughout the nervous system.FMRP is an RNA-binding protein, which interacts with specific neuronal mRNA-targets and with other proteins and is involved in mRNA-transport, stability and translationDrosophila model closely recapitulates the neuronal defects of the clinical disease phenotype and its FMRP homolog (dFMRP) shares similar biochemical features.Using this model and the GAL4/UAS system for targeted gene expression, we performed genetic interaction experiments. We over-expressed the gene dfmr1 (Drosophia fragile X mental retardation 1) in the developing wing imaginal discs and looked for possible suppressor/enhancer effects of the genes scrib(sribbled) and dlg1(discs large 1). We also looked for similar genetic interactions in the adult brain neurons.We found that scrib acted as an enhancer of the mutant wing phenotype, induced by the over-expression of dfmr1. scrib also enhanced the mutant synaptic phenotype in the adult brain neurons, caused by the overexpression or lack of expression of dfmr1.dlg1 had an opposite suppressor effect in both systems analyzed. It rescued the mutant wing phenotype and the mutant synaptic phenotype as well.Our results demonstrate that dfmr1 interacts genetically with the members of the Lg1-family of scaffolding proteins and functions with them in the synaptic architecture of Drosophila adult brain neurons.