PXD031936

PXD031936 is an original dataset announced via ProteomeXchange.

Title	Spatial centrosome proteome of human neural cells uncovers novel interactors and disease hubs
Description	Despite 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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:55:54.413.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD031936
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Fatma Uzbas
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-28 03:33:56	ID requested
1	2022-06-22 03:41:57	announced
⏵ 2	2023-11-14 08:55:55	announced	2023-11-14: Updated project metadata.

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;

submitter keyword: neuron, neural stem cells, neurodevelopmental disorder, human brain, RNA splicing,Centrosome, interactome

Prof. Dr. Magdalena Goetz
contact affiliation	Department of Physiological Genomics, Biomedical Center, Ludwig-Maximilians University, Germany
contact email	magdalena.goetz@helmholtz-muenchen.de
lab head
Fatma Uzbas
contact affiliation	Institute of Stem Cell Research, Helmholtz Center Munich
contact email	fatma.uzbas@helmholtz-muenchen.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/06/PXD031936

PRIDE project URI

• PRIDE
  1. PXD031936
     1. Label: PRIDE project
     2. Name: Spatial centrosome proteome of human neural cells uncovers novel interactors and disease hubs