Cited 14 times since 2022 (7.5 per year) source: EuropePMC Science (New York, N.Y.), Volume 376, Issue 6599, 17 3 2022, Pages eabf9088 Spatial centrosome proteome of human neural cells uncovers disease-relevant heterogeneity. O'Neill AC, Uzbas F, Antognolli G, Merino F, Draganova K, Jäck 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, Götz M
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.
