Presentation description

Synapses facilitate electrochemical signaling between neurons, enabling processes such as sensory, memory, learning, and locomotive control, which are essential for complex cognition and behavior. Synapses are composed of proteins that are either produced pre or post synaptically, however, it's unknown if distantly produced circulating factors (e.g. hormones) target synapses. In this study, we aimed to discover synaptic regulator proteins that are not produced in the synapse by (i) in silico prediction of adipose-secreted proteins that bind extracellular synaptic proteins and (ii) in vivo functional analysis of candidate synaptic regulators in Drosophila melanogaster. For our in-silico prediction screen, we used AlphaFold-Multimer to test for protein-protein binding, computed binding scores using two metrics, and plotted the resulting data using R. For in vivo characterization in Drosophila, we selected an adipose-secreted protein we named Adiposyn, which we predicted to bind to synaptic Neuroligin proteins. Through Drosophila genetics, dissection, and confocal imaging, we are currently testing if Adiposyn is expressed in adipose tissue, localizes to the synapses, is required for normal bouton morphology, and/or is required for adult climbing behavior. We focus on the Drosophila neuromuscular junction (NMJ), which is a well-studied model synapse. The significance of this project is to discover and characterize the functions of circulating protein regulators on synaptic function, thereby identifying drug targets and treatments for neurodevelopmental disorders.