Mutations in certain genes that encode proteins at the synapse, the junctions between neurons, are known to be associated with autism spectrum disorders. Two such families of proteins, neurexins and neuroligins, are thought to be important for assembling synapses. However, the role of these molecules in synapse formation and overall neuronal function is still poorly understood.
Manzoor Bhat and his colleagues at the University of North Carolina are investigating the functions of these proteins in the genetically tractable Drosophila melanogaster (fruit fly) model system. In 2007, they identified the Drosophila orthologs of the mammalian proteins and generated null mutations to eliminate these proteins in the flies. This resulted in structural defects at the neuromuscular synapse and severe behavioral defects in the mutant fly larvae and adults.
Bhat and his team plan to use a combination of genetic, cell biological and electrophysiological methods on the mutants to dissect the molecular mechanisms and genetic pathways that involve neurexins and neuroligins in synapse formation during early development. They plan to use sophisticated strategies to identify genetic modifiers of the phenotypes, as these modifiers may also prove to be candidate genes for autism spectrum disorders.
The researchers hope that their studies in the Drosophila model system will reveal basic molecular clues about how synaptic functions are compromised in neurological disorders such as autism. The information could help in the design of interventions to restore or preserve the delicate functional relationship between pre- and post- synaptic cellular compartments.