Victoria Kreyden Butler University, Kristen Rush Butler University, Morgan Harrison Butler University
Faculty Sponsor(s): Jennifer Kowalski Butler UniversityProper neuronal communication is essential for nervous system function. Communication occurs at specialized junctions, called synapses, where chemical neurotransmitters released from presynaptic neurons bind receptors on postsynaptic cells. Synaptic proteins are tightly regulated; misregulation occurs in neurological diseases, such as epilepsy. One pathway that regulates synaptic proteins is the SUMO (small ubiquitin-like modifier) pathway, which adds small SUMO polypeptide tags to targets; however, the molecular mechanisms by which SUMOylation affects the amount of signaling are unknown. We investigated how SUMO enzymes control synaptic transmission in the Caenorhabditis elegans neuromuscular junction (NMJ). This synapse employs a balance of excitatory (acetylcholine) and inhibitory (GABA) signaling from presynaptic motor neurons to control contraction of postsynaptic muscle cells. We used behavioral assays, loss-of-function techniques, and overexpression studies to examine how the SUMO conjugating enzyme UBC-9 acts in specific neuronal types to control muscle contraction at the NMJ. We found inhibition of UBC-9 in GABA neurons caused increased muscle contraction. Interestingly, overexpression of wild type UBC-9 or catalytically inactive UBC-9 [UBC-9 (C93S)] in GABA neurons also caused increased muscle contraction. This could be due to SUMO-limiting effects on UBC-9; this possibility is being investigated. Increased pre-synaptic accumulation of GFP-tagged synaptic vesicle proteins in GABA neurons of UBC-9 overexpression worms relative to wildtype worms suggests the increased muscle contraction might result from decreased GABA release. Given the similarities between C. elegans and mammalian nervous systems, our results may provide insight related to human neurobiology and may contribute to research on diseases with imbalances in neuronal signaling.
When & Where
Gallahue Hall 102