Cell-specific Protein Degradation Regulates Stress-induced Serotonergic Neuromodulation


September 20, 2017 - 1:00pm
Northwest Building, Room 243
About the Speaker
Xicotencatl Gracida Canales
Speaker Title: 
Research Associate
Speaker Affiliation: 
Zhang and Calarco Labs

Animals modulate behavior in response to experience and the environment. A key link between previous experiences and altered behavior is the neuromodulator serotonin, which transmits information from the environment to alter properties of neural circuits. However, our understanding of how specific neuromodulatory cell types modulate behavior is limited by the complexity of the nervous system. Moreover, despite serotonin importance, the cytoplasmic mechanisms influencing serotonergic neuromodulation in response to stimuli are unclear. To overcome this challenges, we adapted the Translating Ribosome Affinity Purification (TRAP) approach in C. elegans to identify ribosome-associated mRNAs in neuromodulatory dopaminergic and serotonergic cells. From these profiles we found elc-2, an ortholog of the mammalian Elongin C, to be specifically expressed in the ADF serotonergic sensory neurons, a neuronal class involved in stress response.

In this talk I will present our findings showing that in response to stress an E3 ubiquitin-ligase complex formed by Elongin BC–VHL-1 (components of an Elongin-Cullin-SOCS-box or ECS complex) regulates long-lasting changes in feeding behavior through serotonergic neuromodulation. At the cellular level, heat stress induces a redistribution of Elongin C in ADF serotonergic neurons. We are currently investigating the significance of this redistribution for behavioral change. Together, our results characterize the subcellular and dynamic regulation of a conserved E3 ubiquitin ligase in specific neuromodulatory neurons and identify a novel function for ECS-mediated protein degradation in integrating stress signals to regulate serotonergic neuromodulation of lasting behavioral states.