View Program - 63rd Annual Drosophila Research Conference

Synapses are connections between a presynaptic neuron and a postsynaptic cell, proper formation of synapses are needed for neuronal signaling. The ability to make and prune synapses is referred to as structural synaptic plasticity. The perturbation of plasticity is associated with many disease states. We use the Drosophila neuromuscular junction (NMJ) to study synaptic plasticity. Previous work in our lab shows that the Drosophila homolog of Activity-regulated cytoskeleton associated protein (dArc1), a retrovirus-like protein, forms capsids, transfers its own RNA in a viral-like fashion across the NMJ modulates, and finally that this transfer is needed for structural synaptic plasticity. However, the mechanism of how dArc1 regulates plasticity, and how its transfer is involved in this regulation is unknown.
Here, using dArc1 knock downs in motor neurons followed by deep sequencing, we have found a subset of mRNAs that are decreased in muscle .
These represent RNAs that might depend on dArc1 for transfer across the synapse. Using this approach, we found that the Drosophila homolog of muscleblind (mbl) in fly muscles is decreased significantly with dArc1 knocked down in motor neurons. Consistent with a transfer of mbl across the NMJ, over-expression of mbl in the neuron causes a significant increase of mbl RNA both pre- and post- synaptically. Further, co-immunoprecipitation experiments suggest dArc1 protein binds to mbl RNA. Strikingly, both mbl knock down and mblover-expression cause a reduction of structural synaptic plasticity.
Taken together, mbl mRNA is transferred across the NMJ and may be a cargo of dArc1 capsids and genetically it appears mbl is needed for structural synaptic plasticity. We are now investigating if the known functions of Mbl, such as regulating alternative splicing or RNA localization is the mechanism by which changes in Mbl expression affects plasticity.

Identifying New Players in Structural Synaptic Plasticity