{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["O'Connor JT"],"funding":["National Institute of Arthritis and Musculoskeletal and Skin Diseases","American Heart Association","Columbia University","NICHD NIH HHS","National Institute of Genetics","National Cancer Institute","NICHD","NCI NIH HHS","NIAMS NIH HHS","National Institute of General Medical Sciences","NIGMS NIH HHS","National Institute of Child Health and Human Development"],"pagination":["2160-2175.e5"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8367014"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["56(15)"],"pubmed_abstract":["The presence of a wound triggers surrounding cells to initiate repair mechanisms, but it is not clear how cells initially detect wounds. In epithelial cells, the earliest known wound response, occurring within seconds, is a dramatic increase in cytosolic calcium. Here, we show that wounds in the Drosophila notum trigger cytoplasmic calcium increase by activating extracellular cytokines, Growth-blocking peptides (Gbps), which initiate signaling in surrounding epithelial cells through the G-protein-coupled receptor Methuselah-like 10 (Mthl10). Latent Gbps are present in unwounded tissue and are activated by proteolytic cleavage. Using wing discs, we show that multiple protease families can activate Gbps, suggesting that they act as a generalized protease-detector system. We present experimental and computational evidence that proteases released during wound-induced cell damage and lysis serve as the instructive signal: these proteases liberate Gbp ligands, which bind to Mthl10 receptors on surrounding epithelial cells, and activate downstream release of calcium."],"journal":["Developmental cell"],"pubmed_title":["Proteolytic activation of Growth-blocking peptides triggers calcium responses through the GPCR Mthl10 during epithelial wound detection."],"pmcid":["PMC8367014"],"funding_grant_id":["T32 CA119925","5T32CA119925","R21 AR068933","T32HD007502","R01 GM130130","R21 AR072510","T32 HD007502","19PRE34410069","1R01GM130130","R21AR072510"],"pubmed_authors":["O'Connor JT","Narayanan NP","Shannon EK","LaFever KS","Hutson MS","Page-McCaw A","Gailey CD","Stevens AC","Akbar FB"],"additional_accession":[]},"is_claimable":false,"name":"Proteolytic activation of Growth-blocking peptides triggers calcium responses through the GPCR Mthl10 during epithelial wound detection.","description":"The presence of a wound triggers surrounding cells to initiate repair mechanisms, but it is not clear how cells initially detect wounds. In epithelial cells, the earliest known wound response, occurring within seconds, is a dramatic increase in cytosolic calcium. Here, we show that wounds in the Drosophila notum trigger cytoplasmic calcium increase by activating extracellular cytokines, Growth-blocking peptides (Gbps), which initiate signaling in surrounding epithelial cells through the G-protein-coupled receptor Methuselah-like 10 (Mthl10). Latent Gbps are present in unwounded tissue and are activated by proteolytic cleavage. Using wing discs, we show that multiple protease families can activate Gbps, suggesting that they act as a generalized protease-detector system. We present experimental and computational evidence that proteases released during wound-induced cell damage and lysis serve as the instructive signal: these proteases liberate Gbp ligands, which bind to Mthl10 receptors on surrounding epithelial cells, and activate downstream release of calcium.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Aug","modification":"2025-04-05T16:11:08.185Z","creation":"2025-02-19T02:26:19.263Z"},"accession":"S-EPMC8367014","cross_references":{"pubmed":["34273275"],"doi":["10.1016/j.devcel.2021.06.020"]}}