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O'Neill, A.C. ; Uzbas, F. ; Antognolli, G. ; Merino, F.L. ; Draganova, K. ; Jäck, A. ; Zhang, S.* ; Pedini, G.* ; Schessner, J.P.* ; Cramer, K.* ; Schepers, A. ; Metzger, F. ; Esgleas Izquierdo, M. ; Smialowski, P. ; Guerrini, R.* ; Falk, S. ; Feederle, R.* ; Freytag, S.* ; Wang, Z.* ; Bahlo, M.* ; Jungmann, R.* ; Bagni, C.* ; Borner, G.H.H.* ; Robertson, S.P.* ; Hauck, S.M. ; Götz, M.

Spatial centrosome proteome of human neural cells uncovers disease-relevant heterogeneity.

Science 376:eabf9088 (2022)
Verlagsversion DOI PMC
Free by Publisher
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The centrosome provides an intracellular anchor for the cytoskeleton, regulating cell division, cell migration, and cilia formation. We used spatial proteomics to elucidate protein interaction networks at the centrosome of human induced pluripotent stem cell-derived 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 pre-mRNA-processing factor 6 (PRPF6) reproduced the periventricular misplacement in the developing mouse brain, highlighting missplicing of transcripts of a microtubule-associated kinase with 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Sprache englisch
Veröffentlichungsjahr 2022
HGF-Berichtsjahr 2022
ISSN (print) / ISBN 0036-8075
e-ISSN 1095-9203
Zeitschrift Science
Quellenangaben Band: 376, Heft: 6599, Seiten: , Artikelnummer: eabf9088 Supplement: ,
Verlag American Association for the Advancement of Science (AAAS)
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Stem Cell Research (ISF)
CF Monoclonal Antibodies (CF-MAB)
CF Metabolomics & Proteomics (CF-MPC)
POF Topic(s) 30204 - Cell Programming and Repair
30201 - Metabolic Health
30203 - Molecular Targets and Therapies
Forschungsfeld(er) Stem Cell and Neuroscience

Enabling and Novel Technologies
PSP-Element(e) G-500800-001
G-500893-001
A-631900-001
G-505700-001
DOI 10.1126/science.abf9088
WOS ID WOS:000815052900038
Scopus ID 85132454329
PubMed ID 35709258
Erfassungsdatum 2022-07-12
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