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Tomosyn is upregulated by IgE and functions as a PKC-regulated fusion clamp in mast cell degranulation

ABSTRACT: The regulation of soluble N ethylmaleimide sensitive factor attachment receptor (SNARE) mediated membrane fusion by upstream signaling events is poorly understood. Here we show that the SNARE binding protein tomosyn-1 negatively regulates type I IgE Fc receptor (FcRI) induced degranulation of mast cells. After FcRI stimulation, tomosyn-1 (also STXBP5) was phosphorylated on serine and threonine residues and dissociated from the SNARE protein syntaxin 4 (STX4), followed by association with syntaxin 3 (STX3). Protein kinase A (PKA) and protein kinase C (PKC) prevented these activities. We identified PKC as the major kinase required for tomosyn-1 threonine phosphorylation and for the regulation of the interaction with STXs. Incubation with high IgE concentrations induced tomosyn-1 expression in cultured mast cells. In basophils from allergic patients with normal total IgE serum titers tomosyn-1 expression was lower than in patients with high IgE titers who expressed tomosyn-1 to the same extent as non-allergic subjects. Our findings identified tomosyn-1 as a negative regulator of mast cell degranulation that required PKC to switch its interaction with STX partners during fusion. The IgE-mediated upregulation of tomosyn-1 in allergic patients may represent a counter-regulatory mechanism to limit disease development.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Mast Cell

SUBMITTER: Thibaut LEGER

LAB HEAD: Ulrich Blank

PROVIDER: PXD010047 | Pride | 2018-07-04

REPOSITORIES: Pride

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			Action	DRS
	1615004-Q1-CTRL-replicate1.raw	Raw
	1615004-Q10-T0-replicate3.raw	Raw
	1615004-Q11-T3-replicate3.raw	Raw
	1615004-Q12-T9-replicate3.raw	Raw
	1615004-Q2-T0-replicate1.raw	Raw

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