Spatial centrosome proteome of human neural cells uncovers disease-relevant heterogeneity
O'Neill AC, Uzbas F, Antognolli G, Merino F, Draganova K, Jaeck 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, Goetz M (2022)
Publication Type: Journal article
Publication year: 2022
Journal
Book Volume: 376
Article Number: eabf9088
Journal Issue: 6599
Abstract
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.
Involved external institutions
Ludwig-Maximilians-Universität (LMU)
Germany (DE)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Chinese Academy of Sciences (CAS) / 中国科学院
China (CN)
Università degli Studi di Roma 'Tor Vergata'
Italy (IT)
Max-Planck-Institut für Biochemie / Max Planck Institute of Biochemistry
Germany (DE)
Anna Meyer Children’s University Hospital
Italy (IT)
Walter and Eliza Hall Institute of Medical Research (WEHI)
Australia (AU)
University of Otago
New Zealand (NZ)
Germany (DE)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Chinese Academy of Sciences (CAS) / 中国科学院
China (CN)
Università degli Studi di Roma 'Tor Vergata'
Italy (IT)
Max-Planck-Institut für Biochemie / Max Planck Institute of Biochemistry
Germany (DE)
Anna Meyer Children’s University Hospital
Italy (IT)
Walter and Eliza Hall Institute of Medical Research (WEHI)
Australia (AU)
University of Otago
New Zealand (NZ)
How to cite
APA:
O'Neill, A.C., Uzbas, F., Antognolli, G., Merino, F., Draganova, K., Jaeck, A.,... Goetz, M. (2022). Spatial centrosome proteome of human neural cells uncovers disease-relevant heterogeneity. Science, 376(6599). https://doi.org/10.1126/science.abf9088
MLA:
O'Neill, Adam C., et al. "Spatial centrosome proteome of human neural cells uncovers disease-relevant heterogeneity." Science 376.6599 (2022).
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