An Elongin-Cullin-SOCS Box Complex Regulates Stress-Induced Serotonergic Neuromodulation

Publication date: 12 December 2017
Source:Cell Reports, Volume 21, Issue 11
Author(s): Xicotencatl Gracida, Michael F. Dion, Gareth Harris, Yun Zhang, John A. Calarco
Neuromodulatory cells transduce environmental information into long-lasting behavioral responses. However, the mechanisms governing how neuronal cells influence behavioral plasticity are difficult to characterize. Here, we adapted the translating ribosome affinity purification (TRAP) approach in C. elegans to profile ribosome-associated mRNAs from three major tissues and the neuromodulatory dopaminergic and serotonergic cells. We identified elc-2, an Elongin C ortholog, specifically expressed in stress-sensing amphid neuron dual ciliated sensory ending (ADF) serotonergic sensory neurons, and we found that it plays a role in mediating a long-lasting change in serotonin-dependent feeding behavior induced by heat stress. We demonstrate that ELC-2 and the von Hippel-Lindau protein VHL-1, components of an Elongin-Cullin-SOCS box (ECS) E3 ubiquitin ligase, modulate this behavior after experiencing stress. Also, heat stress induces a transient redistribution of ELC-2, becoming more nuclearly enriched. Together, our results demonstrate dynamic regulation of an E3 ligase and a role for an ECS complex in neuromodulation and control of lasting behavioral states.

Graphical abstract

Teaser

Neurons integrate and transmit information from the environment to regulate behavior. Using a cell-specific profiling method, Gracida et al. identify a component of an E3 ubiquitin ligase that is required in serotonergic neurons to regulate feeding behavior after experiencing heat stress. This indicates that protein degradation may integrate stimuli to regulate animal states.


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