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PXD031936

PXD031936 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSpatial centrosome proteome of human neural cells uncovers novel interactors and disease hubs
DescriptionDespite the crucial importance of the centrosome in brain development and disease, its comprehensive proteome remains uncharacterized in neural cells. Here, we used spatial proteomics to elucidate protein interaction networks at the centrosome of iPSC-derived human neural stem cells (NSCs) and neurons. Centrosome-associated proteins were largely cell type-specific, with protein hubs involved in RNA dynamics. Analysis of neurodevelopmental disease cohorts identified a significant overrepresentation of NSC centrosome proteins with variants in patients with periventricular heterotopia (PH). Expressing the PH-associated mutant splicing factor PRPF6 reproduced the periventricular misplacement in the developing mouse brain, highlighting mis-splicing of transcripts of the MAP-kinase SAD-A at centrosomal location as essential for the phenotype. Collectively, cell type-specific centrosome interactomes explain how genetic variants in ubiquitous proteins may convey brain-specific phenotypes.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:55:54.413.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD031936
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterFatma Uzbas
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-02-28 03:33:56ID requested
12022-06-22 03:41:57announced
22023-11-14 08:55:55announced2023-11-14: Updated project metadata.
Publication List
O'Neill AC, Uzbas F, Antognolli G, Merino F, Draganova K, J, ä, ck A, Zhang S, Pedini G, Schessner JP, Cramer K, Schepers A, Metzger F, Esgleas M, Smialowski P, Guerrini R, Falk S, Feederle R, Freytag S, Wang Z, Bahlo M, Jungmann R, Bagni C, Borner GHH, Robertson SP, Hauck SM, G, ö, tz M, Spatial centrosome proteome of human neural cells uncovers disease-relevant heterogeneity. Science, 376(6599):eabf9088(2022) [pubmed]
10.6019/PXD031936;
Keyword List
submitter keyword: neuron, neural stem cells, neurodevelopmental disorder, human brain, RNA splicing,Centrosome, interactome
Contact List
Prof. Dr. Magdalena Goetz
contact affiliationDepartment of Physiological Genomics, Biomedical Center, Ludwig-Maximilians University, Germany
contact emailmagdalena.goetz@helmholtz-muenchen.de
lab head
Fatma Uzbas
contact affiliationInstitute of Stem Cell Research, Helmholtz Center Munich
contact emailfatma.uzbas@helmholtz-muenchen.de
dataset submitter
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Dataset FTP location
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PRIDE project URI
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