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PXD036167

PXD036167 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCyclosporine A Modulates LSP1 Protein Levels in Human B Cells to Attenuate B Cell Migration at Low O2 Levels
DescriptionCoordinated migration of B cells within and between secondary lymphoid tissues is required for robust antibody responses to infection or vaccination. Secondary lymphoid tissues normally expose B cells to a low O2 (hypoxic) environment. Recently, we have shown that human B cell migration is modulated by an O2-dependent molecular switch, centrally controlled by the hypoxia-induced (transcription) factor-1a (HIF1A), which can be disrupted by the immunosuppressive calcineurin inhibitor, cyclosporine A (CyA). However, the mechanisms by which low O2 environments attenuate B cell migration remain poorly defined. Proteomics analysis has linked CXCR4 chemokine receptor signaling to cytoskeletal rearrangement. We now hypothesize that the pathways linking the O2 sensing molecular switch to chemokine receptor signaling and cytoskeletal rearrangement would likely contain phosphorylation events, which are typically missed in traditional transcriptomic and/or proteomic analyses. Hence, we have performed a comprehensive phosphoproteomics analysis of human B cells treated with CyA after engagement of the chemokine receptor CXCR4 with CXCL12. Statistical analysis of the separate and synergistic effects of CyA and CXCL12 revealed 116 proteins whose abundance is driven by a synergistic interaction between CyA and CXCL12. Among these 116 proteins, Lymphocyte Specific Protein 1 (LSP1) was most interesting due to its original identification as a protein modulating neutrophil migration. We used our previously described algorithm BONITA to reveal a critical role for LSP1 in cytoskeletal rearrangement. Validating these modeling results, we show experimentally that LSP1 levels in B cells increase with low O2 exposure, and CyA treatment results in decreased LSP1 protein levels. This correlates with the increased chemotactic activity observed after CyA treatment. Lastly, we directly link LSP1 levels to chemotactic capacity, as shRNA knock-down of LSP1 results in significantly increased B cell chemotaxis at low O2 levels. These results directly link the CyA to LSP1-dependent cytoskeletal regulation, demonstrating a previously unrecognized mechanism by which CyA modulates human B cell migration.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:58:05.195.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterShichen Shen
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-08-19 01:29:08ID requested
12022-08-24 11:56:33announced
22023-11-14 08:58:05announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: chemotaxis, CXCR4,human B cells, LSP1
Contact List
Jun Qu
contact affiliationDepartment of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, USA
contact emailjunqu@buffalo.edu
lab head
Shichen Shen
contact affiliationUniversity at Buffalo
contact emailshichens@buffalo.edu
dataset submitter
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