PXD028974

PXD028974 is an original dataset announced via ProteomeXchange.

Title	A longer isoform of Stim1 is a negative SOCE regulator but increases cAMP modulated NFAT signaling
Description	Alternative splicing is a potent modifier of protein function. Stromal interaction molecule 1 (Stim1) is the essential activator of store-operated Ca2+ entry (SOCE) triggering activation of transcription factors. Here, we characterize Stim1A, a splice variant with an additional 31 amino acid domain inserted in frame within its cytosolic domain. Prominent expression of exon A is found in astrocytes, heart, kidney and testes. Full length Stim1A functions as a dominant-negative regulator of SOCE and ICRAC, facilitating sequence specific fast calcium dependent inactivation and destabilizing gating or Orai1. Downregulation or absence of native Stim1A results in increased SOCE. Despite reducing SOCE, Stim1A leads to increased NFAT translocation. Differential proteomics revealed interference of Stim1A with the cAMP-SOCE crosstalk by altered modulation of phosphodiesterase (PDE8B), resulting in reduced cAMP degradation and increased PIP5K activity, facilitating an increased NFAT activation. Our study uncovers a hitherto unknown mechanism regulating NFAT activation and indicates that cell type specific splicing of Stim1 is a potent means to regulate the NFAT signalosome and cAMP-SOCE crosstalk.
HostingRepository	PRIDE
AnnounceDate	2021-11-11
AnnouncementXML	Submission_2021-11-11_02:51:21.274.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Zimmer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-07 00:21:40	ID requested
⏵ 1	2021-11-11 02:51:21	announced

Dataset with its publication pending

submitter keyword: NFAT, Orai, PDE8, PIP2, splicing

Barbara Niemeyer
contact affiliation	Center for Integrative Physiology and Molecular Medicine (CIPMM), Bld. 48, Saarland University
contact email	Barbara.Niemeyer@uks.eu
lab head
David Zimmer
contact affiliation	TU KL - CSB
contact email	davidzimmer91@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028974
     1. Label: PRIDE project
     2. Name: A longer isoform of Stim1 is a negative SOCE regulator but increases cAMP modulated NFAT signaling