PXD042189-1

PXD042189 is an original dataset announced via ProteomeXchange.

Title	Mercury intoxication disrupts tonic signaling in B cells, and may promote autoimmunity due to abnormal phosphorylation of STIM-1 and other autoimmunity risk associated phosphoproteins involved in BCR signaling
Description	Epidemiological studies link exposure to mercury with autoimmune disease. Unfortunately, in spite of considerable effort, no generally accepted mechanistic understanding of how mercury actually functions with respect to the etiology of autoimmune disease is currently available. Nevertheless, autoimmune disease often arises because of defective B cell signaling. Because B cell signaling is dependent on phosphorylation cascades, in this report, we have focused on how mercury intoxication alters phosphorylation of B cell proteins in antigen-non stimulated (tonic) mouse splenic B cells. Specifically, we utilized mass spectrometric techniques to conduct a comprehensive unbiased global analysis of the effect of mercury on the entire B cell phosphoproteome. We found that the effects were pleotropic in the sense that large numbers of pathways were impacted. However, confirming our earlier work, we found that the B cell signaling pathway stood out from the rest, in that phosphoproteins which had sites which were affected by mercury, exhibited a much higher degree of connectivity, than components of other pathways. Further analysis showed that many of these BCR pathway proteins had been previously linked to autoimmune disease. Finally, dose response analysis of these BCR pathway proteins showed STIM1_S575, and NFAT2_S259 are the two most mercury sensitive of these sites. Because STIM1_S575 controls the ability of STIM1 to regulate internal Ca2+, we speculate that STIM1 may be the initial point of disruption, where mercury interferes with B cell signaling leading to systemic autoimmunity, with the molecular effects pleiotropically propagated throughout the cell by virtue of Ca2+ dysregulation.
HostingRepository	PRIDE
AnnounceDate	2024-10-17
AnnouncementXML	Submission_2024-10-17_04:06:52.013.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD042189
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Maurgan Lee
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue; monohydroxylated residue; deaminated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-12 08:37:47	ID requested
⏵ 1	2024-10-17 04:06:52	announced

Carruthers NJ, Guo C, Gill R, Stemmer PM, Rosenspire AJ, Mercury intoxication disrupts tonic signaling in B cells, and may promote autoimmunity due to abnormal phosphorylation of STIM-1 and other autoimmunity risk associated phosphoproteins involved in BCR signaling. Toxicol Appl Pharmacol, 474():116607(2023) [pubmed]

10.1016/j.taap.2023.116607;

10.6019/PXD042189;

submitter keyword: mercury, phosphorylation, autoimmunity, phospho-serine, B cells, BCR, immunotoxicity, STIM1

Allen Rosenspire
contact affiliation	Wayne State University
contact email	arosenspire@med.wayne.edu
lab head
Maurgan Lee
contact affiliation	Wayne State University
contact email	mightymo@wayne.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042189
     1. Label: PRIDE project
     2. Name: Mercury intoxication disrupts tonic signaling in B cells, and may promote autoimmunity due to abnormal phosphorylation of STIM-1 and other autoimmunity risk associated phosphoproteins involved in BCR signaling