{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:02:10Z","timestamp":1781103730277,"version":"3.54.1"},"reference-count":72,"publisher":"American Society for Clinical Investigation","issue":"6","funder":[{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"crossref","award":["R01HL129795"],"award-info":[{"award-number":["R01HL129795"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"crossref","award":["R41HL136057"],"award-info":[{"award-number":["R41HL136057"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"crossref","award":["NIDDK DK065988"],"award-info":[{"award-number":["NIDDK DK065988"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"crossref","award":["R01HL080396"],"award-info":[{"award-number":["R01HL080396"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"crossref","award":["R01HL130938"],"award-info":[{"award-number":["R01HL130938"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"crossref","award":["R21ES023384"],"award-info":[{"award-number":["R21ES023384"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"crossref","award":["DICKEY15P0"],"award-info":[{"award-number":["DICKEY15P0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"crossref","award":["DICKEY18G0"],"award-info":[{"award-number":["DICKEY18G0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"crossref","award":["KREDA13G0"],"award-info":[{"award-number":["KREDA13G0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"crossref","award":["KREDA16XX0"],"award-info":[{"award-number":["KREDA16XX0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"crossref","award":["BOUCHER15R0"],"award-info":[{"award-number":["BOUCHER15R0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"crossref"}]},{"name":"U.S. Department of Defense","award":["PR160247"],"award-info":[{"award-number":["PR160247"]}]},{"name":"Cancer Center Support","award":["NCI-CA016672(GEMF)"],"award-info":[{"award-number":["NCI-CA016672(GEMF)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,3,21]]},"abstract":"<jats:p>Airway mucin secretion is necessary for ciliary clearance of inhaled particles and pathogens but can be detrimental in pathologies such as asthma and cystic fibrosis. Exocytosis in mammals requires a Munc18 scaffolding protein, and airway secretory cells express all 3 Munc18 isoforms. Using conditional airway epithelial cell\u2013deletant mice, we found that Munc18a has the major role in baseline mucin secretion, Munc18b has the major role in stimulated mucin secretion, and Munc18c does not function in mucin secretion. In an allergic asthma model, Munc18b deletion reduced airway mucus occlusion and airflow resistance. In a cystic fibrosis model, Munc18b deletion reduced airway mucus occlusion and emphysema. Munc18b deficiency in the airway epithelium did not result in any abnormalities of lung structure, particle clearance, inflammation, or bacterial infection. Our results show that regulated secretion in a polarized epithelial cell may involve more than one exocytic machine at the apical plasma membrane and that the protective roles of mucin secretion can be preserved while therapeutically targeting its pathologic roles.<\/jats:p>","DOI":"10.1172\/jci.insight.124815","type":"journal-article","created":{"date-parts":[[2019,2,5]],"date-time":"2019-02-05T12:03:35Z","timestamp":1549368215000},"source":"Crossref","is-referenced-by-count":14,"title":["Different Munc18 proteins mediate baseline and stimulated airway mucin secretion"],"prefix":"10.1172","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8089-4275","authenticated-orcid":true,"given":"Ana M.","family":"Jaramillo","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA."},{"name":"Institute of Bioscience and Technology, Texas A&M University Health Science Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Piccotti","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter V.","family":"Velasco","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5098-8163","authenticated-orcid":true,"given":"Anna Sofia Huerta","family":"Delgado","sequence":"additional","affiliation":[{"name":"Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Mexico."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoulikha","family":"Azzegagh","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicity","family":"Chung","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute\/Cystic Fibrosis Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usman","family":"Nazeer","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0039-3767","authenticated-orcid":true,"given":"Junaid","family":"Farooq","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josh","family":"Brenner","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4464-8744","authenticated-orcid":true,"given":"Jan","family":"Parker-Thornburg","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenton L.","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5600-7314","authenticated-orcid":true,"given":"Christopher M.","family":"Evans","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver School of Medicine, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0146-0768","authenticated-orcid":true,"given":"Roberto","family":"Adachi","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan R.","family":"Burns","sequence":"additional","affiliation":[{"name":"College of Optometry, University of Houston, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia M.","family":"Kreda","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute\/Cystic Fibrosis Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8126-7716","authenticated-orcid":true,"given":"Michael J.","family":"Tuvim","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4780-1847","authenticated-orcid":true,"given":"Burton F.","family":"Dickey","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2019,3,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0910061"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.70.113006.100702"},{"issue":"11","key":"B3","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a009597","article-title":"Supramolecular dynamics of mucus","volume":"2","author":"Verdugo","year":"2012","journal-title":"Cold Spring Harb Perspect Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nature12807"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00015.2016"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1013660"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00004.2016"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2005-0460OC"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2006-0180OC"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20102057"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe0706634"},{"key":"B12","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms7281","article-title":"The polymeric mucin Muc5ac is required for allergic airway hyperreactivity","volume":"6","author":"Evans","year":"2015","journal-title":"Nat Commun"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.70.113006.100638"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0127267"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.149310"},{"issue":"279","key":"B16","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.2003755","article-title":"Mechanosensitive ATP release maintains proper mucus hydration of airways","volume":"6","author":"Button","year":"2013","journal-title":"Sci Signal"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2006-0060OC"},{"issue":"5 Pt 1","key":"B18","doi-asserted-by":"crossref","first-page":"C1313","DOI":"10.1152\/ajpcell.1992.262.5.C1313","article-title":"Goblet cell degranulation in isolated canine tracheal epithelium: response to exogenous ATP, ADP, and adenosine","volume":"262","author":"Davis","year":"1992","journal-title":"Am J Physiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M807849200"},{"issue":"3","key":"B20","doi-asserted-by":"crossref","DOI":"10.1042\/BSR20150004","article-title":"SNAP23 is selectively expressed in airway secretory cells and mediates baseline and stimulated mucin secretion","volume":"35","author":"Ren","year":"2015","journal-title":"Biosci Rep"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.222091"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biophys-060414-034057"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20120057"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5454.864"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.3.638"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.002455"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2004.03503.x"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.02.014"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2009.04.002"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-513-8_17"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2007-0279RC"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1300109"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1172\/JCI73469"},{"issue":"9","key":"B34","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a009589","article-title":"CFTR, mucins, and mucus obstruction in cystic fibrosis","volume":"2","author":"Kreda","year":"2012","journal-title":"Cold Spring Harb Perspect Med"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/nm1028"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.18.13476"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201506112"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611318104"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200812026"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-10-535831"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.409649"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/36882"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.2337\/db12-1380"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.361501"},{"key":"B45","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2018.00529","article-title":"Bi-allelic mutations in STXBP2 reveal a complementary role for STXBP1 in cytotoxic lymphocyte killing","volume":"9","author":"Lopez","year":"2018","journal-title":"Front Immunol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.186668"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA117.000792"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.1.379-388.2000"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201806-371AW"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.06.043"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E17-02-0117"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1172\/JCI84910"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2013.09.004"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.08.113"},{"issue":"26","key":"B55","doi-asserted-by":"crossref","first-page":"6842","DOI":"10.1073\/pnas.1703228114","article-title":"Gel-forming mucins form distinct morphologic structures in airways","volume":"114","author":"Ostedgaard","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"B56","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.124863","article-title":"Mucus strands from submucosal glands initiate mucociliary transport of large particles","volume":"4","author":"Fischer","year":"2019","journal-title":"JCI Insight"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2013-0050OC"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2016.07.004"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2004-0060OC"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2818.2010.03481.x"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.816884"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/nature11234"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1038\/nature11209"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.66.11.4605-4614.2000"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/ismej.2012.8"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq461"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2604"},{"issue":"Database issue","key":"B70","first-page":"D590","article-title":"The SILVA ribosomal RNA gene database project: improved data processing and web-based tools","volume":"41","author":"Quast","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.222091"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006670"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/124815\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:32:24Z","timestamp":1779193944000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/124815"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,21]]},"references-count":72,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2019,3,21]]},"published-print":{"date-parts":[[2019,3,21]]}},"alternative-id":["10.1172\/jci.insight.124815"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.124815","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/451914","asserted-by":"object"}]},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,21]]},"article-number":"e124815"}}