{"doi":"10.7554/elife.49917","title":"An alternatively spliced, non-signaling insulin receptor modulates insulin sensitivity via insulin peptide sequestration in C. elegans","abstract":"In the nematode C. elegans, insulin signaling regulates development and aging in response to the secretion of numerous insulin peptides. Here, we describe a novel, non-signaling isoform of the nematode insulin receptor (IR), DAF-2B, that modulates insulin signaling by sequestration of insulin peptides. DAF-2B arises via alternative splicing and retains the extracellular ligand binding domain but lacks the intracellular signaling domain. A daf-2b splicing reporter revealed active regulation of this transcript through development, particularly in the dauer larva, a diapause stage associated with longevity. CRISPR knock-in of mScarlet into the daf-2b genomic locus confirmed that DAF-2B is expressed in vivo and is likely secreted. Genetic studies indicate that DAF-2B influences dauer entry, dauer recovery and adult lifespan by altering insulin sensitivity according to the prevailing insulin milieu. Thus, in C. elegans alternative splicing at the daf-2 locus generates a truncated IR that fine-tunes insulin signaling in response to the environment.","journal":"eLife","year":2020,"id":99760,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":339578,"name":"Pedro R. Rodrigues","orcid":"0000-0002-1539-3017","position":1,"is_corresponding":false},{"id":491375,"name":"Ricardo M Nuñez Medina","orcid":null,"position":2,"is_corresponding":false},{"id":490580,"name":"Prosenjit Mondal","orcid":"0000-0001-8566-249X","position":3,"is_corresponding":false},{"id":490581,"name":"Neale Harrison","orcid":"0000-0001-6821-4089","position":4,"is_corresponding":false},{"id":490582,"name":"Museer A. Lone","orcid":"0000-0001-9710-775X","position":5,"is_corresponding":false},{"id":491376,"name":"Amanda Webster","orcid":null,"position":6,"is_corresponding":false},{"id":233164,"name":"Aditi U. Gurkar","orcid":"0000-0003-4338-0624","position":7,"is_corresponding":false},{"id":348130,"name":"Brock Grill","orcid":"0000-0002-0379-3267","position":8,"is_corresponding":false},{"id":490583,"name":"Matthew S. Gill","orcid":"0000-0003-0818-8792","position":9,"is_corresponding":false},{"id":490579,"name":"Bryan Martinez","orcid":"0000-0002-0133-0306","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T22:38:09.754371Z","pmid":"32096469","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}