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PXD052439

PXD052439 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleGlobal proteomics and affinity mass spectrometry analysis of human Schwann cells indicates that loss of NF1 alters cellular and mitochondrial metabolism - Global
DescriptionDetailed global proteomics analysis for NF1 deficient cells and tissues is lacking. We investigated proteomes from immortalized human Schwann cells with (+/+) and without (-/-) NF1 to evaluate potential biomarkers and targets in NF1 deficient cells. We identified over 1900 proteins in both cell lines and find 148 proteins with differential expression levels based on genotype. Following Ingenuity Pathway analysis (IPA), we found multiple pathways were altered including decrease in “oxidative phosphorylation,” increases in “mitochondrial dysfunction”, and “glycolysis”, as well as changes in “Myelination Signaling Pathway.” Next, we stably transfected NF1 -/- cells with tagged mNf1 cDNAs (either WT or variant) and again evaluated the global proteome. We identified an overall trend of metabolic differences pertaining to oxidative phosphorylation, mitochondria dysfunction, and glycolysis in the mutant cDNA expressing cells compared to WT cDNA cells. We then validated differential expression of the following proteins: LAMC1, CYB5R3, and SOD2. Additionally, we used the encoded Strep tag on the cDNA to affinity purity NF1 Protein-Protein interactors from the Schwann cells expressing WT and variant cDNAs. We were able to identify 98 PPIs and 9 overlap with prior HEK293 cell datasets while 89 are unique to Schwann cells. GO analysis indicates many of these PPIs play a role in protein-transporting ATP synthase complex or are involved with intermediate filaments. While we were able to show that some of these bind differentially to variant isoforms, variations within NF1 did not significantly impact ability to bind partners. Finally, we show that loss of NF1 impacts Schwann cell mitochondrial respiration via Seahorse validating our proteomics data and indicating that NF1 plays a significant role in in mitochondrial metabolism that results in proteomics changes in Schwann cells.
HostingRepositoryPRIDE
AnnounceDate2025-05-07
AnnouncementXMLSubmission_2025-05-06_17:14:55.567.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterjames mobley
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-05-21 06:20:14ID requested
12025-05-06 17:14:56announced
Publication List
10.1038/s41598-024-84493-y;
Fay CX, Zunica ERM, Awad E, Bradley W, Church C, Liu J, Liu H, Crossman DK, Mobley JA, Kirwan JP, Axelrod CL, Westin E, Kesterson RA, Wallis D, Global proteomics and affinity mass spectrometry analysis of human Schwann cells indicates that variation in and loss of neurofibromin (NF1) alters protein expression and cellular and mitochondrial metabolism. Sci Rep, 15(1):3883(2025) [pubmed]
Keyword List
submitter keyword: Systems Analysis,NF1, LCMS, Proteomics
Contact List
James Mobley
contact affiliationUAB CCC MS Proteomics Facility
contact emailmobleyja@uab.edu
lab head
james mobley
contact affiliationUniversity of Alabama at Birmingham
contact emailmobleyja@uab.edu
dataset submitter
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Dataset FTP location
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