Elly Mawi Butler University, Victoria Kreyden Butler University, Kristen Rush Butler University, Morgan Harrison Butler University
Faculty Sponsor(s): Jennifer Kowalski Butler UniversityThe nervous system relies on tight protein regulation to maintain a balance of excitatory to inhibitory signaling to ensure proper function. SUMO (small ubiquitin-like modifier) polypeptides are attached to proteins by the UBC-9 conjugating enzyme to regulate processes including neuronal signaling. Multiple neuronal proteins are SUMOylated, including several implicated in neurodegenerative diseases; yet, the mechanisms by which SUMOylation affects neuronal signaling balance remain unknown. We are investigating how SUMO enzymes control synaptic transmission in Caenorhabditis elegans at the neuromuscular junction (NMJ), a specialized synapse where a balance of excitatory (acetylcholine) and inhibitory (GABA) signaling from presynaptic motor neurons controls postsynaptic muscle contraction. We hypothesized UBC-9 acts in presynaptic motor neurons to control signaling via its SUMO-conjugating activity. Neither overexpression nor inhibition of UBC-9 in cholinergic neurons affected neuromuscular activity. However, knockdown or overexpression of UBC-9 in all neurons or exclusively in GABA neurons caused muscle hypercontraction. Thus, proper UBC-9 levels in GABA neurons appear required to control NMJ signaling. Worms expressing a catalytically inactive mutant of UBC-9 in GABA neurons also displayed increased muscle excitation, suggesting SUMO-conjugating activity may not be required for UBC-9's effects. Imaging results indicate both green fluorescent protein tagged UBC-9 (GFP::UBC-9) or SMO-1 (GFP::SMO-1) can localize with red synaptic vesicle proteins at inhibitory neuromuscular presynapses. Current studies are investigating the role of UBC-9's catalytic site for UBC-9's NMJ effects. Given the similarities between C. elegans and mammalian nervous systems, understanding how SUMO enzymes control E:I balance may provide critical information related to human neurobiology and disease.
When & Where
Gallahue Hall 105