The centrosome is the organelle responsible for the organization of the cytoskeleton during cell division, an essential function in organisms from yeast to humans. Until now, scientists assumed that the centrosome was very similar in all cells due to its general tasks. However, a research team evaluated this notion in neurons and their developmental precursors, so-called neuronal stem cells.
“There is so much we don't yet know about these cells, including how the centrosomes of neurons compare to those of neural stem cells and other cell types,” the senior author says. Their subsequent discoveries now fundamentally challenge the assumption that all centrosomes are created equal.
The researchers found that the composition of proteins in centrosomes differs profoundly depending on the cell type. “We were surprised not only by the unexpected high degree of heterogeneity of the centrosomes, but also by the discovery of many unexpected proteins associated with them – for example, RNA-binding proteins and even proteins responsible for splicing (the processing of RNA), which normally takes place in the nucleus,” the author explains:
The scientists discovered that a specific protein (the ubiquitously expressed splicing protein PRPF6) is enriched at the centrosome in neural stem cells, but not in neurons. A mutation of the protein found in patients with brain malformation periventricular heterotopia also leads to a similar phenotype in animal models.
The author concludes, “This means that the location of a protein is crucial for a disease. With our centrosome analysis, we now have an important resource to test further associations with neuronal diseases. In particular, our research can explain for the first time why a protein that is present in all cells, after mutation, causes a phenotype only in the brain, but not in other organs. This will allow further insights into disease mechanisms – and thus get one step closer to their treatment.”
Can centrosome heterogeneity in human neural cells be linked to diseases?
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