{"id":237161,"date":"2026-05-14T19:11:46","date_gmt":"2026-05-15T00:11:46","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2026\/05\/a-neuropeptide-regulates-cell-non-autonomous-protein-homeostasis"},"modified":"2026-05-14T19:11:46","modified_gmt":"2026-05-15T00:11:46","slug":"a-neuropeptide-regulates-cell-non-autonomous-protein-homeostasis","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2026\/05\/a-neuropeptide-regulates-cell-non-autonomous-protein-homeostasis","title":{"rendered":"A neuropeptide regulates cell non-autonomous protein homeostasis"},"content":{"rendered":"

<\/a><\/p>\n

FLP-17\u2019s role in stress resistance aligns with its established functions. FLP-17 belongs to an evolutionarily conserved class, FMRF-amide\/RF-amide neuropeptides, that plays important roles in energy balance and reproduction across phyla.34<\/sup><\/a>,<\/sup>35<\/sup><\/a> In C<\/i>. elegans<\/i>,<\/i> FLP-17 is secreted from a pair of sensory neurons (BAG) in response to low oxygen and high carbon dioxide, which can be caused by unfavorable food conditions or pathogens.36<\/sup><\/a>,<\/sup>37<\/sup><\/a> FLP-17 then acts through specific neurons to inhibit egg laying and initiate an aversion behavior until the animal has reached more favorable conditions.30<\/sup><\/a>,<\/sup>36<\/sup><\/a> Interestingly, unfavorable food conditions and pathogens also threaten organismal protein homeostasis.33<\/sup><\/a>,<\/sup>38<\/sup><\/a> Therefore, we speculate that FLP-17 evolved to simultaneously protect the animal from proteotoxic stress while facilitating a behavioral program to help the animal navigate to more favorable conditions.<\/p>\n

To coordinate adaptive behavioral and metabolic responses, FLP-17 primarily signals through the GPCR EGL-6 in specific neurons.30<\/sup><\/a>,<\/sup>31<\/sup><\/a> Therefore, we tested whether EGL-6 also mediates FLP-17\u2019s role in UPRER<\/sup> activation and found that FLP-17-induced activation of the UPRER<\/sup> and ER stress resistance is partially dependent on EGL-6. Egl-6<\/i> expression is predominantly neuronal, evidenced by transcriptional reporters and single-cell RNA-seq datasets.30<\/sup><\/a>,<\/sup>39<\/sup><\/a> However, low levels of egl-6<\/i> expression were detected in intestine-specific translation of ribosome-affinity purification, which may better reflect protein levels.40<\/sup><\/a> This suggests that FLP-17 may signal either through an intermediate cell type (such as a neuron) or directly to the intestine to activate UPRER<\/sup>.30<\/sup><\/a>,<\/sup>39<\/sup><\/a> Furthermore, the partial dependence, combined with persistent stress gene activation in egl-6 <\/i>(lof<\/i>) backgrounds (Figure 5 <\/a>E), indicates that additional unidentified receptors and mechanisms likely contribute to FLP-17 phenotypes.<\/p>\n

Although FLP-17 was sufficient to activate the UPRER<\/sup>, it was not required for cell non-autonomous activation of the UPRER<\/sup> by glial:: xbp-1s<\/i><\/i>,<\/i> as flp-17<\/i> null mutants did not suppress glial:: xbp-1s<\/i><\/i> phenotypes. This likely reflects neuropeptide network redundancy. Supporting this hypothesis, flp-17 <\/i>(lof)) resulted in modest upregulation of stress response genes (Figure S3G) and a slight increase in hsp-4p::GFP<\/i> in the glial:: xbp-1s<\/i><\/i> animals (Figure 2D), suggesting compensatory activation of stress signaling pathways when FLP-17 is absent. This compensation could occur through multiple mechanisms. First, glial:: xbp-1s<\/i><\/i> may induce multiple neuropeptides that provide functionally redundant UPRER<\/sup> activation. While no other candidate from our neuropeptidomics screen was individually sufficient to induce UPRER<\/sup>, we cannot exclude compensation by peptides not detected in our analysis, such as insulin-like peptides.<\/p>\n","protected":false},"excerpt":{"rendered":"

FLP-17\u2019s role in stress resistance aligns with its established functions. FLP-17 belongs to an evolutionarily conserved class, FMRF-amide\/RF-amide neuropeptides, that plays important roles in energy balance and reproduction across phyla.34,35 In C. elegans, FLP-17 is secreted from a pair of sensory neurons (BAG) in response to low oxygen and high carbon dioxide, which can be [\u2026]<\/p>\n","protected":false},"author":662,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1506,6],"tags":[],"class_list":["post-237161","post","type-post","status-publish","format-standard","hentry","category-food","category-robotics-ai"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/237161","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/662"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=237161"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/237161\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=237161"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=237161"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=237161"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}