{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T18:02:16Z","timestamp":1785348136343,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.pgen.1012240","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000}}],"reference-count":71,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK108801"],"award-info":[{"award-number":["R01 DK108801"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["T32 AG029796"],"award-info":[{"award-number":["T32 AG029796"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    Insulin \/ insulin-like growth factor signaling (IIS) in\n                    <jats:italic>C. elegans<\/jats:italic>\n                    is mediated by the DAF-2 receptor and insulin-like peptides (ILP) that can act as agonists or antagonists. DAF-2 signaling is also affected by DAF-2B, a truncated, non-signaling, secreted isoform of DAF-2 that acts as a decoy receptor by sequestering ILPs. In this study, we performed a forward genetic screen for modifiers of DAF-2B protein expression and identified a mutation in\n                    <jats:italic>unc-31<\/jats:italic>\n                    that increased DAF-2B\n                    <jats:italic>.<\/jats:italic>\n                    UNC-31 is involved in dense core vesicle docking and is required for neuropeptide secretion, including ILPs. As a result,\n                    <jats:italic>unc-31<\/jats:italic>\n                    mutants constitutively enter the dauer larval stage and are long-lived due to reduced IIS. We find that increased nervous system DAF-2B accumulation is associated with reduced agonist ILP availability, in both\n                    <jats:italic>unc-31<\/jats:italic>\n                    mutants and wild type worms. Using auxin-induced degradation (AID) and fluorescence lifetime imaging microscopy-F\u00f6rster resonance energy transfer (FLIM-FRET), we find that a significant fraction of nervous system DAF-2B is in the form of a heterodimeric complex with a full-length DAF-2 receptor isoform, representing a new class of DAF-2 hybrid receptor. In\n                    <jats:italic>unc-31<\/jats:italic>\n                    mutants, DAF-2B also undergoes endocytosis in neurons in an AP2-dependent manner and genetic manipulation of\n                    <jats:italic>daf-2b<\/jats:italic>\n                    in the\n                    <jats:italic>unc-31<\/jats:italic>\n                    mutant suggests that DAF-2B homodimers may function to reinforce a reduced insulin signaling state by clearing agonist ILPs from the extracellular space. These findings indicate that DAF-2B not only forms homodimers, but also hybrid receptors with full-length DAF-2, to regulate the activity of the large and diverse family of ILPs in\n                    <jats:italic>C. elegans<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1012240","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T19:14:46Z","timestamp":1784834086000},"page":"e1012240","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Partitioning of the truncated insulin receptor DAF-2B between homodimers and heterodimers influences insulin signaling in C. elegans"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0133-0306","authenticated-orcid":true,"given":"Bryan 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