Expression and transcriptional regulation of Munc18 isoforms in mast cells.

Mast cells are specialized immune cells with a central pathophysiological role in allergic reactions and important roles in pathogen defense. Their main effector response is the exocytic release of preformed inflammatory mediators from secretory granules. Munc18 proteins are essential for exocytic function, so we analyzed the expression of Munc18 transcripts in RBL-2H3 mast cells and mouse bone marrow derived mast cells (BMMC). All three isoforms of Munc18 are expressed in both cell types, but Munc18-2 transcripts are most abundant. The proximal 181 bp region of the Munc18-2 gene promoter is conserved between mice and humans, and shows maximal promoter activity among a series of truncation mutants. Binding sites for Ets, E-box and CREB transcription factors that are known to be important for mast cell development are highly conserved and functionally active. Thus, mast cells upregulate an essential component of their exocytic machinery as they develop morphologic and functional features of the regulated secretory phenotype.