Bachelor of Science (Honors), University of Victoria, 2005 (Victoria BC, Canada)
I am particularly interested in understanding how synaptic transmission can be modulated by G-protein ßγ subunits. Activation of Gi/o-coupled GPCRs has been shown play an important role in regulating neurotransmitter release through the actions of Gßγ subunits. Our lab has recently identified an entirely novel regulatory mechanism of Gßγ-mediated inhibition of exocytosis which occurs distal to calcium entry. We have shown that Gßγ subunits can directly interact with the exocytotic machinery to inhibit evoked transmitter release and have shown that this mechanism limits both the number and duration of fusion events in both central synapses and chromaffin cell large dense core granules. Despite this, very little is known about the prevalence of this interaction at a synapse or its physiological relevance. Thus, the central goal of my research is to evaluate the specificity and functional significance of this mechanism in order to delineate both the specific molecular requirements and the mechanism of action for Gßγ-SNARE interactions.
Betke KM, Wells CA, and Hamm HE. GPCR mediated regulation of synaptic transmission. Progress in Neurobiology. 2012. Mar: 96(304-321)
Wells CA, Betke KM, Lindsley CW, and Hamm HE. Label-free detection of G protein-SNARE interactions and screening for small molecule modulators. ACS Chemical Neuroscience. 2012. Jan 18; 3(1): 69-78.