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Ratnesh Singh, Yasutake Mori, Shingo Miyata, Masaya Tohyama, Visvanathan Ramamurthy; Retinal Horizontal cell numbers are modulated by neuron specific methyl transferase, PRMT8. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2450.
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Arginine methylation is a common posttranslational protein modification found in eukaryotic cells. This modification is catalyzed by family of enzymes called protein arginine methyltransferases (PRMTs). These enzymes are thought to regulate gene expression through methylation of histone and non histone proteins. PRMTs are distributed ubiquitously throughout the body including neurons. Among PRMTs, PRMT8 is unique as it is selectively present in the neurons. PRMT8 shares 80% homology with PRMT1 and is proposed to function as heterodimer. In this study, we focused on the role for arginine methylation by PRMT8 in development and function of retinal neurons.
We checked subcellular distribution of PRMT8 and PRMT1 in mouse retina by immunohistochemistry. To understand the function of Prmt8 in retina we generated a complete knockout of Prmt8 in mice. Electroretinographic recordings were used to assess the physiological role of Prmt8 in retina. We examined horizontal cell number by whole mount staining with calbindin antibody and cone cell numbers by a combination of opsin and peanut agglutinin staining.
PRMT8 staining was confined to cone photoreceptors, horizontal cell nuclei and processes, subset of amacrine cells and inner plexiform layer. Co-labeling study with cell type specific markers and absence of PRMT8 signal in knockout animals confirmed our PRMT8 localization in retina. PRMT1, a close homologue of PRMT8 was found mainly in all inner nuclei and ganglion cells indicating a distribution pattern that is different than PRMT8. Interestingly, our preliminary study showed an increase (40%) in horizontal cell density in central part of retina in animal lacking PRMT8 compared to littermate controls. Increase in horizontal cell density was supported by increased levels of calbindin by western blotting.
Our results demonstrate that PRMT8 and PRMT1 localization differs in the retina suggesting that each enzyme has a unique functional role independent of other. Additionally our results showing differences in the horizontal cell number in animals lacking PRMT8 suggest that intercellular spacing and density of horizontal cells may be controlled by epigenetic mechanisms or post translational protein modification by arginine methylation.
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