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

Authors
 Kyubo KIM ; Youlia M. PETROVA ; Burton F. DICKEY ; Michael J. TUVIM ; Roberto ADACHI ; James A. MCNEW ; Joo-Heon YOON ; Binhui REN ; Lucia PICCOTTI ; Rustam BAGIRZADEH ; Vesa M. OLKKONEN ; Elsa M. RODARTE ; Alejandra GOMEZ ; Zoulikha AZZEGAGH ; Christopher M. EVANS ; Anurag AGRAWAL ; Rupesh NIGAM ; Brenton L. SCOTT 
Citation
 Biochemical Journal, Vol.446(3) : 383~394, 2012 
Journal Title
 Biochemical Journal 
ISSN
 0264-6021 
Issue Date
2012
Abstract
Airway 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 anaphylaxis was 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 identify Munc18b as an essential gene that is a limiting component of the exocytic machinery of epithelial cells and MCs.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/89715
DOI
10.1042/BJ20120057
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Otorhinolaryngology
Yonsei Authors
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