Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455.
J Cell Biol. 2014 Jan 6;204(1):95-109. doi: 10.1083/jcb.201306071. Epub 2013 Dec 30.
As they initiate migration in vertebrate embryos, neural crest cells are enriched for methylation cycle enzymes, including S-adenosylhomocysteine hydrolase (SAHH), the only known enzyme to hydrolyze the feedback inhibitor of trans-methylation reactions. The importance of methylation in neural crest migration is unknown. Here, we show that SAHH is required for emigration of polarized neural crest cells, indicating that methylation is essential for neural crest migration. Although nuclear histone methylation regulates neural crest gene expression, SAHH and lysine-methylated proteins are abundant in the cytoplasm of migratory neural crest cells. Proteomic profiling of cytoplasmic, lysine-methylated proteins from migratory neural crest cells identified 182 proteins, several of which are cytoskeleton related. A methylation-resistant form of one of these proteins, the actin-binding protein elongation factor 1 alpha 1 (EF1α1), blocks neural crest migration. Altogether, these data reveal a novel and essential role for post-translational nonhistone protein methylation during neural crest migration and define a previously unknown requirement for EF1α1 methylation in migration.
在脊椎动物胚胎中启动迁移时，神经嵴细胞富含甲基化循环酶，包括 S-腺苷同型半胱氨酸水解酶 (SAHH)，这是唯一已知的能够水解转甲基反应反馈抑制剂的酶。甲基化在神经嵴迁移中的重要性尚不清楚。在这里，我们表明 SAHH 对于极化的神经嵴细胞的迁出是必需的，这表明甲基化对于神经嵴迁移是必不可少的。尽管核组蛋白甲基化调节神经嵴基因表达，但 SAHH 和赖氨酸甲基化蛋白在迁移的神经嵴细胞的细胞质中大量存在。从迁移的神经嵴细胞中细胞质、赖氨酸甲基化蛋白的蛋白质组学分析鉴定了 182 种蛋白质，其中一些与细胞骨架有关。这些蛋白质中的一种的甲基化抗性形式，即肌动蛋白结合蛋白伸长因子 1α1 (EF1α1)，阻止了神经嵴的迁移。总之，这些数据揭示了在神经嵴迁移过程中翻译后非组蛋白蛋白质甲基化的新的和必需的作用，并定义了 EF1α1 甲基化在迁移中的以前未知的要求。
