Munc18b is an essential gene in mice whose expression is limiting for secretion by airway epithelial and mast cells

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dc.citation.firstpage383en_US
dc.citation.journalTitleBiochemical Journalen_US
dc.citation.lastpage394en_US
dc.citation.volumeNumber446en_US
dc.contributor.authorKim, Kyuboen_US
dc.contributor.authorPetrova, Youlia M.en_US
dc.contributor.authorScott, Brenton L.en_US
dc.contributor.authorNigam, Rupeshen_US
dc.contributor.authorAgrawal, Anuragen_US
dc.contributor.authorEvans, Christopher M.en_US
dc.contributor.authorAzzegagh, Zoulikhaen_US
dc.contributor.authorGomez, Alejandraen_US
dc.contributor.authorRodarte, Elsa M.en_US
dc.contributor.authorOlkkonen, Vesa M.en_US
dc.contributor.authorBagirzadeh, Rustamen_US
dc.contributor.authorPiccotti, Luciaen_US
dc.contributor.authorRen, Binhuien_US
dc.contributor.authorYoon, Joo-Heonen_US
dc.contributor.authorMcNew, James A.en_US
dc.contributor.authorAdachi, Robertoen_US
dc.contributor.authorTuvim, Michael J.en_US
dc.contributor.authorDickey, Burton F.en_US
dc.contributor.funderCystic Fibrosis Foundationen_US
dc.contributor.funderNational Institutes of Healthen_US
dc.date.accessioned2013-04-01T16:00:37Zen_US
dc.date.available2013-04-01T16:00:37Zen_US
dc.date.issued2012en_US
dc.description.abstractAirway mucin secretion and MC (mast cell) degranulation must be tightly controlled for homoeostasis of the lungs and immune system respectively. We found the exocytic protein Munc18b to be highly expressed in mouse airway epithelial cells and MCs, and localized to the apical pole of airway secretory cells. To address its functions, we created a mouse with a severely hypomorphic Munc18b allele such that protein expression in heterozygotes was reduced by∼50%. Homozygous mutant mice were not viable, but heterozygotes showed a ∼50% reduction in stimulated release of mucin from epithelial cells and granule contents from MCs. The defect in MCs affected only regulated secretion and not constitutive or transporter-mediated secretion. The severity of passive cutaneous anaphylaxiswas also reduced by ∼50%, showing that reduction of Munc18b expression results in an attenuation of physiological responses dependent on MC degranulation. The Munc18b promoter is controlled by INR (initiator), Sp1 (specificity protein 1), Ets, CRE (cAMP-response element), GRE (glucocorticoid-response element), GATA and E-box elements in airway epithelial cells; however, protein levels did not change during mucous metaplasia induced by allergic inflammation. Taken together, the results of the present study identifyMunc18b as an essential gene that is a limiting component of the exocytic machinery of epithelial cells and MCs.en_US
dc.embargo.termsnoneen_US
dc.identifier.citationKim, Kyubo, Petrova, Youlia M., Scott, Brenton L., et al.. "Munc18b is an essential gene in mice whose expression is limiting for secretion by airway epithelial and mast cells." <i>Biochemical Journal,</i> 446, (2012) 383-394. http://dx.doi.org/10.1042/BJ20120057.en_US
dc.identifier.doihttp://dx.doi.org/10.1042/BJ20120057en_US
dc.identifier.grantID08GO (Cystic Fibrosis Foundation)en_US
dc.identifier.grantIDHL094848 (National Institutes of Health)en_US
dc.identifier.grantIDHL097000 (National Institutes of Health)en_US
dc.identifier.grantIDHL072984 (National Institutes of Health)en_US
dc.identifier.grantIDCA16672 (National Institutes of Health)en_US
dc.identifier.grantIDAI093533 (National Institutes of Health)en_US
dc.identifier.urihttps://hdl.handle.net/1911/70880en_US
dc.language.isoengen_US
dc.publisherPortland Press Limiteden_US
dc.subject.keywordexocytosisen_US
dc.subject.keywordmast cellen_US
dc.subject.keywordmucinen_US
dc.subject.keywordmucusen_US
dc.subject.keywordMunc18en_US
dc.subject.keywordsecretionen_US
dc.titleMunc18b is an essential gene in mice whose expression is limiting for secretion by airway epithelial and mast cellsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
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