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

Abstract

Summary 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 ADF serotonergic sensory neurons, and 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-CullinSOCS-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.

Coordinated Activity of Transcriptional Networks Responding to the Pattern of Action Potential Firing in Neurons

“…This likely shows a change in transcriptional priorities and calcium signaling in the simulated cells from cellular metabolic activity signature seen in the unstimulated condition to a more focused genetic signature related to the decoding of external signals. In support of this hypothesis it has recently been demonstrated that the activity of transcription factor Tceb1 is regulated by experience dependent neuronal plasticity driven by specific external stimuli in Caenorhabditis elegans [34]. Tceb1 is a transcriptional regulator of transcription elongation, therefore it has the capacity to be a common regulator of many genes, including calcium signaling genes, which are controlled by neuronal activity firing patterns.…”

Two isoforms of the essential C. elegans Argonaute CSR-1 differentially regulate sperm and oocyte fertility

“…Table S6). In contrast, only 6/119 and 1/119 up-regulated genes were present in the muscle and neuronal TRAP data sets (Gracida et al, 2017), respectively (Fig. 5D, Supp.…”

“…Conversely, the genes displaying increased expression showed a weak association with muscle, intestine, and neuronal GO terms (data not shown). To understand which tissues or processes the upregulated genes were associated with, we examined several additional datasets, including modENCODE mRNA-seq data from each stage of development, Translating Ribosome Affinity Purification (TRAP) data from muscles, neurons, and intestines (Gracida et al, 2017), and sperm proteome data (Ma et al, 2014) (Supp. Table S6).…”

“…Venn-pie diagrams comparing genes that are differentially expressed in csr-1a(tor159), gfp::3xflag::csr-1b (inner circle) with gene sets that define spermatogenesis-enriched transcripts, oogenesis-enriched transcripts, and gender neutral transcripts (enriched in both spermatogenesis and oogenesis) (Ortiz et al, 2014), and germline expressed sRNAs (as determined by genes that are 2 fold or more depleted of sRNAs in glp-4(bn2) mutants) (Gracida et al, 2017), and the sperm proteome genes (Ma et al, 2014). Numbers in bold indicate statistically significant overlap as calculated by Fisher's Exact Test, p<0.001.…”

Serotonin signaling by maternal neurons upon stress ensures progeny survival

“…30 infection. Similarly, exposure to increasing temperatures enhances 5-HT release from the 54 serotonergic neurons (called NSM and ADF neurons) through the activity of the animal's 55 thermosensory neurons (called AFD neurons) and this release of 5-HT cell non-autonomously 56 protects the animal from proteotoxicity (Gracida, Dion, Harris, Zhang, & Calarco, 2017; Iwanir 57 et al, 2016; Shao et al, 2019; Tatum et al, 2015a). However, whether 5-HT released by the 58 parent upon the detection of stress protects germ cells and future progeny from stress is not 59 known.…”