PRMT8 as a phospholipase regulates Purkinje cell dendritic arborization and motor coordination.
Jun-Dal KimKyung-Eui ParkJunji IshidaKoichiro KakoJuri HamadaShuichi KaniMiki TakeuchiKana NamikiHajime FukuiShigetomo FukuharaMasahiko HibiMakoto KobayashiYasunori KanahoYoshitoshi KasuyaNaoki MochizukiAkiyoshi FukamizuPublished in: Science advances (2015)
The development of vertebrate neurons requires a change in membrane phosphatidylcholine (PC) metabolism. Although PC hydrolysis is essential for enhanced axonal outgrowth mediated by phospholipase D (PLD), less is known about the determinants of PC metabolism on dendritic arborization. We show that protein arginine methyltransferase 8 (PRMT8) acts as a phospholipase that directly hydrolyzes PC, generating choline and phosphatidic acid. We found that PRMT8 knockout mice (prmt8 (-/-)) displayed abnormal motor behaviors, including hindlimb clasping and hyperactivity. Moreover, prmt8 (-/-) mice and TALEN-induced zebrafish prmt8 mutants and morphants showed abnormal phenotypes, including the development of dendritic trees in Purkinje cells and altered cerebellar structure. Choline and acetylcholine levels were significantly decreased, whereas PC levels were increased, in the cerebellum of prmt8 (-/-) mice. Our findings suggest that PRMT8 acts both as an arginine methyltransferase and as a PC-hydrolyzing PLD that is essential for proper neurological functions.
Keyphrases
- nitric oxide
- induced apoptosis
- single cell
- spinal cord
- spinal cord injury
- stem cells
- type diabetes
- cell proliferation
- cell therapy
- skeletal muscle
- metabolic syndrome
- mesenchymal stem cells
- drug induced
- endothelial cells
- small molecule
- cell death
- insulin resistance
- endoplasmic reticulum stress
- wild type
- pi k akt
- binding protein