PXD010047

PXD010047 is an original dataset announced via ProteomeXchange.

Title	Tomosyn is upregulated by IgE and functions as a PKC-regulated fusion clamp in mast cell degranulation
Description	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 (FcRI) induced degranulation of mast cells. After FcRI 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.
HostingRepository	PRIDE
AnnounceDate	2018-07-04
AnnouncementXML	Submission_2018-07-04_06:00:17.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thibaut LEGER
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue; acetylated residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2018-06-06 07:20:03	ID requested
⏵ 1	2018-07-04 06:00:18	announced

Dataset with its publication pending

curator keyword: Biological

submitter keyword: immunoprepicipitations, mouse, Q-Exactive plus, mast cells, IgE FC receptor, phosphorylations

Ulrich Blank
contact affiliation	Dr. Ulrich Blank Department chair and team leader Mast cells and Basophils in Inflammation and Remodeling Inserm U 1149 & CNRS ERL8252 Université Paris-Diderot Faculté de Médecine Site X. Bichat 16, rue Henri Huchard F-75870 Paris Cedex 18 FRANCE
contact email	ulrich.blank@inserm.fr
lab head
Thibaut LEGER
contact affiliation	Institut Jacques Monod
contact email	thibaut.leger@ijm.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD010047
     1. Label: PRIDE project
     2. Name: Tomosyn is upregulated by IgE and functions as a PKC-regulated fusion clamp in mast cell degranulation