Chaperoning of closed syntaxin-3 through Lys46 and Glu59 in domain 1 of Munc18 proteins is indispensable for mast cell exocytosis

Journal of Cell Science
Na-Ryum BinShuzo Sugita

Abstract

Understanding how Munc18 proteins govern exocytosis is crucial because mutations of this protein cause severe secretion deficits in neuronal and immune cells. Munc18-2 has indispensable roles in the degranulation of mast cell, partly by binding and chaperoning a subset of syntaxin isoforms. However, the key syntaxin that, crucially, participates in the degranulation – whose levels and intracellular localization are regulated by Munc18-2 – remains unknown. Here, we demonstrate that double knockdown of Munc18-1 and Munc-2 in mast cells results in greatly reduced degranulation accompanied with strikingly compromised expression levels and localization of syntaxin-3. This phenotype is fully rescued by wild-type Munc18 proteins but not by the K46E, E59K and K46E/E59K mutants of Munc-18 domain 1, each of which exhibits completely abolished binding to 'closed' syntaxin-3. Furthermore, knockdown of syntaxin-3 strongly impairs degranulation. Collectively, our data argue that residues Lys46 and Glu59 of Munc18 proteins are indispensable for mediating the interaction between Munc18 and closed syntaxin-3, which is essential for degranulation by chaperoning syntaxin-3. Our results also indicate that the functional contribution of these resid...Continue Reading

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Citations

Mar 5, 2016·Cell Biology International·Satoshi TadokoroNaoko Utsunomiya-Tate
Jun 10, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Na-Ryum BinShuzo Sugita
Aug 23, 2017·The Biochemical Journal·Matthew Grant ArnoldHao Xu 徐昊

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