顺丁酸受体1信号传递相互依赖于亚细胞局部化和细胞代谢
Aenne-Dorothea Liebing1, Philipp Rabe1, Petra Krumbholz1
1Rudolf Schönheimer Institute of Biochemistry, Medical Faculty, Leipzig University, Germany.
酸盐受体1 (SUCNR1) 信号受细胞代谢的影响,影响炎症和能量平衡. 它的位置和激活取决于能量来源,如葡萄糖或谷氨酸.
科学领域:
- 细胞代谢和信号通路.
- G蛋白结合受体 (GPCR) 的功能.
- 免疫代谢和炎症.
背景情况:
- 酸盐是三碳酸循环中的一个关键代谢物.
- 苏酸激活了苏酸受体1 (SUCNR1),这是一个Gi-和Gq-结合的受体.
- SUCNR1信号传递报告了矛盾的抗炎或促炎作用.
研究的目的:
- 为了研究细胞代谢和SUCNR1信号局部化之间的联系.
- 了解不同能量基质如何影响SUCNR1激活和下游信号.
- 解决关于苏克辛酸在炎症中的作用的相互矛盾的报告.
主要方法:
- 基于生物发光共振能量转移 (BRET) 的生物传感器.
- 动态质量再分配 (DMR) 的测量.
- 第二信使测定,激酶酸化测定和成像.
- 在不同能量基质 (葡萄糖/谷氨胺) 下进行代谢分析.
主要成果:
- SUCNR1的信号传递,局部化和细胞代谢是相互依存的.
- 谷氨胺的消费增强了氧化酸化,增加了细胞外的酸盐和SUCNR1内部化.
- SUCNR1表现出不同的Gi/Gq蛋白激活,这取决于空间定位和能量基质.
- SUCNR1与内体内G蛋白相互作用.
- 在M2类巨细胞中,SUCNR1介导的Gi信号刺激糖解,而Gq信号抑制了它.
结论:
- 细胞代谢状态决定了SUCNR1的空间信号传递.
- SUCNR1信号调节细胞能量平衡,以响应酸盐水平.
- 代谢背景对于理解SUCNR1在炎症和细胞功能中的多种作用至关重要.
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