Caprin1 and FMRP Genetically Interact to Regulate the Development of the Larval Drosophila Neuromuscular Junction

Fragile X Syndrome (FXS) is the most prevalent inherited neurodevelopmental disorder worldwide and the most common signal gene cause of autism. Lack of FMRP causes the synaptic phenotype associated with FXS. It is known that RNA-binding proteins like FMRP usually do not act alone and have several binding partners. Caprin1 was identified as a possible binding partner that physically interacts with FMRP by an experiment performed in the Barbee laboratory at the University of Denver. The objective of the current project was to determine if Caprin1 and FMRP genetically interact and regulate synaptic development in Drosophila, a fruit fly. Drosophila is a well-understood model system for studying FXS because the genes for both FMR1 and Caprin1 are homologous to humans. Mutated copies of FMR1 and Caprin1 were crossed into a genetic line, micro-dissected, stained, and imaged by scanning confocal microscopy then statistically compared against control lines. If they interact it was expected to see significant synaptic overgrowth at the neuromuscular junction. The synapses were analogous to the overgrowth seen in the FXS brain. Thus, FMR1 and Caprin1 interact genetically to regulate the synaptic development of the neuromuscular junction in the fruit fly. It is also clear that Caprin1 has a function in synaptogenesis, whether it is pre- or post-synaptic or both would be a direction for future research. There is currently no cure for FXS and limited therapeutics. To develop better therapeutics and a potential cure the underlying mechanisms of the disease must be understood. Thus, the more known about the mechanisms and how the involved proteins function within the cell is beneficial to the scientific and general population altogether. Ultimately, the interaction between FMRP and Caprin1 could provide a possible therapeutic target for investigation and this research has provided insight into the happenings at the cellular level in FXS.