Amano Genki, Matsuzaki Shinsuke, Mori Yasutake, Miyoshi Ko, Han Sarina, Shikada Sho, Takamura Hironori, Yoshimura Takeshi, Katayama Taiichi
Department of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Department of Pharmacology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0012, Japan.
Mol Biol Cell. 2020 Aug 15;31(18):1963-1973. doi: 10.1091/mbc.E20-02-0100. Epub 2020 Jun 17.
Arginine methylation is a common posttranslational modification that modulates protein function. SCY1-like pseudokinase 1 (SCYL1) is crucial for neuronal functions and interacts with γ-COP to form coat protein complex I (COPI) vesicles that regulate Golgi morphology. However, the molecular mechanism by which SCYL1 is regulated remains unclear. Here, we report that the γ-COP-binding site of SCYL1 is arginine-methylated by protein arginine methyltransferase 1 (PRMT1) and that SCYL1 arginine methylation is important for the interaction of SCYL1 with γ-COP. PRMT1 was colocalized with SCYL1 in the Golgi fraction. Inhibition of PRMT1 suppressed axon outgrowth and dendrite complexity via abnormal Golgi morphology. Knockdown of SCYL1 by small interfering RNA (siRNA) inhibited axon outgrowth, and the inhibitory effect was rescued by siRNA-resistant SCYL1, but not SCYL1 mutant, in which the arginine methylation site was replaced. Thus, PRMT1 regulates Golgi morphogenesis via SCYL1 arginine methylation. We propose that SCYL1 arginine methylation by PRMT1 contributes to axon and dendrite morphogenesis in neurons.
精氨酸甲基化是一种常见的翻译后修饰，可调节蛋白质功能。类SCY1假激酶1（SCYL1）对神经元功能至关重要，并与γ-COP相互作用形成调节高尔基体形态的衣被蛋白复合物I（COPI）囊泡。然而，SCYL1的调控分子机制仍不清楚。在此，我们报告SCYL1的γ-COP结合位点被蛋白精氨酸甲基转移酶1（PRMT1）精氨酸甲基化，且SCYL1精氨酸甲基化对SCYL1与γ-COP的相互作用很重要。PRMT1与SCYL1在高尔基体部分共定位。抑制PRMT1通过异常的高尔基体形态抑制轴突生长和树突复杂性。用小干扰RNA（siRNA）敲低SCYL1抑制轴突生长，而这种抑制作用可被抗siRNA的SCYL1挽救，但不能被精氨酸甲基化位点被替换的SCYL1突变体挽救。因此，PRMT1通过SCYL1精氨酸甲基化调节高尔基体形态发生。我们提出PRMT1介导的SCYL1精氨酸甲基化有助于神经元轴突和树突的形态发生。
