Science (New York, N.Y.) · 2022
Spatial centrosome proteome of human neural cells uncovers disease-relevant heterogeneity.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
O'Neill Adam C, Uzbas Fatma, Antognolli Giulia, Merino Florencia, Draganova Kalina, Jäck Alex, Zhang Sirui, Pedini Giorgia, Schessner Julia P, Cramer Kimberly, Schepers Aloys, Metzger Fabian, Esgleas Miriam, Smialowski Pawel, Guerrini Renzo, Falk Sven, Feederle Regina, Freytag Saskia, Wang Zefeng, Bahlo Melanie, Jungmann Ralf, Bagni Claudia, Borner Georg H H, Robertson Stephen P, Hauck Stefanie M, Götz Magdalena
Аннотация
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.