SCYL1 arginine methylation by PRMT1 is key for neuronal development
A group of researchers from Osaka University has discovered that protein arginine methyltransferase 1 (PRMT1), an enzyme that in humans is encoded by the PRMT1 gene, regulates morphogenesis of the Golgi apparatus, an organelle found in most eukaryotic cells. They also clarified that SCY1-like pseudokinase 1 (SCYL1), which is associated with spinocerebellar neurodegeneration (SCD) and controls the development of neural cells, was arginine-methylated by PRMT1.
Proteins, an essential part of all living organisms, are constantly synthesized in cells. Arginine is an important amino acid for optimal growth and development and increases growth hormone levels. PRMT1, a major enzyme that catalyzes the methylation of arginine residues within proteins, is present in cells but its role in the Golgi apparatus was unknown.
Protein arginine methylation is a common post-translational modification and can regulate protein-protein interactions. Previous studies showed that PRMT1 was critical for brain development; however, it was unknown what protein was arginine-methylated by PRMT1 in brain development.
Proteins synthesized in cells are processed in the Golgi apparatus and are transported to their appropriate destination through the cell. The structure of a Golgi apparatus affects its function. Although structural changes and functional disorder of the Golgi apparatus are involved in neurodegenerating diseases such as Alzheimer's disease, Golgi morphology regulation is not well known.
In this study, the researchers aimed to unravel the molecular mechanisms behind the relationship between Golgi morphology and arginine methylation by PRMT1. Recent studies have reported that SCYL1 is required for maintaining the Golgi morphology.
This group investigated whether SCYL1 was arginine-methylated by PRMT1 and found: (1) SCYL1 proteins was arginine-methylated by PRMT1, (2) abnormal Golgi morphology occurs if SCYL1, which maintains Golgi structure and functions, is not arginine-methylated, and (3) arginine methylation of SCYL1 (by PRMT1) was necessary for the development of neural cells (axon outgrowth) from the mouse brain during early embryonic stage. These findings suggest that SCYL1 arginine methylation by PRMT1 is essential for brain development.
This group clarified Golgi morphology regulation mechanisms through arginine methylation of SCYL1, demonstrating the importance of arginine methylation of proteins. Their achievements will lead to the clarification of pathogenetic mechanisms of diseases caused by abnormal Golgi morphology and the establishment of treatment for these diseases.
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The article, " SCYL1 arginine methylation by PRMT1 is essential for neurite outgrowth via Golgi morphogenesis," was published in Molecular Biology of the Cell at DOI: https://www.molbiolcell.org/doi/10.1091/mbc.E20-02-0100.
