在SARM1 TIR域产生的糖循环ADPR分子作为次要产品
Jeremy Garb1, Gil Amitai1, Allen Lu2,3
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
PloS one
|April 18, 2024
概括
无菌的α和TIR含动机1 (SARM1) 蛋白质通过降解尼古丁胺胺氨基二核酸 (NAD+) 来触发编程的轴突死亡. 这项研究揭示了SARM1也产生糖循环ADP-ribose (gcADPR),这是一种可能参与细胞死亡过程的分子.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 无菌阿尔法和TIR动机含有1 (SARM1) 是编程轴突死亡的关键调节器,这个过程被称为瓦勒尔变性.
- SARM1主要通过尼古丁胺胺氨基二核酸 (NAD+) 的降解来调解瓦莱尔变性.
- 新出现的证据表明,SARM1在启动编程轴突死亡时可能具有超出NAD+耗尽的额外功能.
研究的目的:
- 为了研究SARM1在NAD+降解之外的潜在的新型酶活性.
- 为了识别和描述在NAD+代谢过程中由SARM1的TIR域产生的小产物.
- 探索这些新型产品在SARM1介导的编程细胞死亡中的潜在作用.
主要方法:
- 生物化学试验使用来自人类和Drosophila melanogaster的净化SARM1 TIR域.
- 酶活性测试分析NAD+的转化.
- 使用分析技术识别和描述反应产品.
主要成果:
- SARM1 TIR域主要将NAD+转化为ADP-核糖酶 (ADPR) 或循环ADP-核糖酶 (cADPR).
- 观察到小但一致的1′-2′和1′-3′糖循环ADP-ribose (gcADPR) 分子的产生 (~0.1-0.5%的NAD+).
- 在体外和细菌表达系统中证实了gcADPR的产生.
结论:
- 在NAD+代谢过程中,SARM1具有酶活性,产生gcADPR作为次要产物.
- gcADPR是细菌和植物编程细胞死亡途径中已知的第二信使.
- 这些发现表明gcADPR在动物SARM1诱导的编程轴突死亡中的潜在作用,需要进一步调查.
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