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

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.

SEEK ID: http://lmmeisd-2.srv.mwn.de/publications/58

PubMed ID: 35709258

DOI: 10.1126/science.abf9088

Projects: Published Datasets

Publication type: Journal

Journal: Science (New York, N.Y.)

Citation: Science (New York, N.Y.),376(6599):eabf9088

Date Published: 17th Jun 2022

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Registered Mode: manually

Authors: Adam C O'Neill, Fatma Uzbas, Giulia Antognolli, Florencia Merino, Kalina Draganova, Alex Jäck, Sirui Zhang, Giorgia Pedini, Julia P Schessner, Kimberly Cramer, Aloys Schepers, Fabian Metzger, Miriam Esgleas, Pawel Smialowski, Renzo Guerrini, Sven Falk, Regina Feederle, Saskia Freytag, Zefeng Wang, Melanie Bahlo, Ralf Jungmann, Claudia Bagni, Georg H H Borner, Stephen P Robertson, Stefanie M Hauck, Magdalena Götz

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Citation
O’Neill, A. C., Uzbas, F., Antognolli, G., Merino, F., Draganova, K., Jäck, A., Zhang, S., Pedini, G., Schessner, J. P., Cramer, K., Schepers, A., Metzger, F., Esgleas, M., Smialowski, P., Guerrini, R., Falk, S., Feederle, R., Freytag, S., Wang, Z., … Götz, M. (2022). Spatial centrosome proteome of human neural cells uncovers disease-relevant heterogeneity. In Science (Vol. 376, Issue 6599). American Association for the Advancement of Science (AAAS). https://doi.org/10.1126/science.abf9088
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Created: 14th Oct 2024 at 12:53

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