人类血白细胞中化学受体TAS1R3和mGlu2的异构化
Lena Ball1,2, Julia Bauer2, Dietmar Krautwurst2
1TUM School of Life Sciences, Technical University of Munich, Alte Akademie 8a, 85354 Freising, Germany.
International journal of molecular sciences
|August 26, 2023
概括
免疫细胞利用新型味觉受体异构体,特别是甲基胺2 (mGlu2) 和TAS1R3,来检测像MSG这样的乌玛米化合物. 这一发现揭示了通过味觉受体调节免疫反应的新途径.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 与G蛋白结合的受体 (GPCRs) 是一种
背景情况:
- 常规味道受体 (TAS1R2 / TAS1R3表示甜,TAS1R1 / TAS1R3表示乌玛米) 和甲基转移性谷氨酸受体 (mGlu) 存在于免疫细胞中.
- 这些受体属于C类GPCRs,在它们的家族中形成异构体,并在免疫细胞功能中发挥作用.
- 单谷氨酸 (MSG) 是mGlu受体和TAS1R1/TAS1R3乌玛米受体的共享配体.
研究的目的:
- 为了研究mGlu受体和TAS1Rs在白细胞中的受体家族之间潜在的异构化.
- 确定这种跨家族异构体是否具有功能性,并参与免疫细胞信号传递.
主要方法:
- 免疫细胞化学和共免疫沉/西部斑分析以检测血液白细胞中的受体共定位和异构化.
- 在HEK-293细胞中进行生物发光共振能量转移 (BRET) 试验,以验证重组受体的异构化.
- 发光测试用于评估MSG诱导的信号和百日咳毒素的敏感性.
- 使用特定受体对抗剂来评估异体在中性粒细胞IL-8分泌中的作用.
主要成果:
- 甲基胺2 (mGlu2) 和TAS1R3受体在人类血白细胞中共同定位和异构.
- 在HEK-293细胞中形成的重组mGlu2 / TAS1R3异构体,并表现出MSG诱导的咳毒素敏感信号.
- mGlu2 / TAS1R3异构体对于MSG介导的IL-8分泌在与N-formyl-methionyl-leucyl-phenylalanine刺激的中性粒细胞中的增强至关重要和足够.
结论:
- 在白细胞中证明了mGlu2和TAS1R3受体的异构化,形成了一个新的功能化传感单元.
- 表明,独特的化学感知受体组合可以量身定制,以调节特定的细胞免疫反应.
- 突出了一个新的机制,通过这种机制,味觉受体通路可以影响先天免疫力.
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