{"doi":"10.1101/2025.08.15.670582","title":"THE NEUROPEPTIDE NEUROMEDIN U RECEPTOR NMUR-1 BUFFERS INSULIN RECEPTOR SIGNALING IN BACTERIA-DEPENDENT <i>C. ELEGANS</i> SURVIVAL","abstract":"Abstract Distinct microbial environments exert diverse effects on the physiology and survival of the nematode Caenorhabditis elegans . Here, we show that C. elegans grown on two Escherichia coli strains exhibit different survival dynamics. Wild-type C. elegans on the B type OP50 exhibit more early deaths compared to C. elegans on K-12 type CS180. These early deaths on OP50 are characterized by swollen pharynges (P-deaths) due to bacterial accumulation within the tissue. In contrast, animals on CS180 are more resistant to P-deaths. These bacteria-dependent differences in P-deaths depend on bacterial lipopolysaccharide structures and the activities of the C. elegans neuropeptide neuromedin U receptor NMUR-1, which reduces P-deaths on OP50, but not on CS180. Surprisingly, however, NMUR-1 promotes the opposite response when the insulin receptor DAF-2 has reduced function — where NMUR-1 now stimulates P-deaths on OP50, but again with no effect on CS180. We also find that NMUR-1 acts in sensory neurons to promote its bi-directional effects on longevity, which depend on the FOXO transcription factor DAF-16. In addition, NMUR-1 downregulates the expression of the insulin-like peptide daf-28 , but only when DAF-2 function is not reduced. This suggests a regulatory mechanism through which NMUR-1 maintains insulin receptor DAF-2 signaling at a suitable level. Thus, our studies reveal that NMUR-1 serves to buffer the dynamic range of DAF-2 receptor signaling, thereby optimizing pharyngeal health and survival in response to specific bacteria.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":573105,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9602,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":373334,"name":"Bianca Pereira","orcid":"0000-0002-6734-3580","position":1,"is_corresponding":false},{"id":1480325,"name":"Christina DeGregory","orcid":null,"position":2,"is_corresponding":false},{"id":1480326,"name":"Rahi Shah","orcid":null,"position":3,"is_corresponding":false},{"id":383851,"name":"Wolfgang Maier","orcid":"0000-0002-9464-6640","position":4,"is_corresponding":false},{"id":1480327,"name":"Joanne Guan","orcid":null,"position":5,"is_corresponding":false},{"id":1479953,"name":"Ian M. Clark","orcid":"0000-0003-2619-0896","position":6,"is_corresponding":false},{"id":383859,"name":"Dhaval Patel","orcid":"0000-0002-5744-568X","position":7,"is_corresponding":false},{"id":521809,"name":"Quee-Lim Ch'ng","orcid":"0000-0003-1941-3828","position":8,"is_corresponding":false},{"id":364125,"name":"Joy Alcedo","orcid":"0000-0002-5279-6640","position":9,"is_corresponding":false},{"id":1479952,"name":"Deniz Sifoglu","orcid":"0009-0006-2834-3488","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:57:32.445190Z","pmid":"40894749","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":[]}