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S-Geranylgeranyl-L-glutathione是人类B细胞封闭受体P2RY8的配体
Erick Lu1, Finn D Wolfreys1, Jagan R Muppidi1,2
1Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, CA, USA.
Nature
|March 8, 2019
概括
研究人员确定S-geranylgeranyl-L-glutathione (GGG) 是P2RY8受体的一个新型配体,对调节生殖中心B细胞封闭至关重要,并且与B细胞恶性瘤有关.
科学领域:
- 免疫学和癌症生物学
- 分子和细胞生物学
背景情况:
- 生殖中心对适应性免疫至关重要,但也与B细胞癌症有关.
- 限制毛囊内移动性生殖中心B细胞的机制尚未完全理解.
- 参与B细胞迁移和生长的P2RY8受体在B细胞淋巴瘤中经常发生突变.
研究的目的:
- 为了确定P2RY8受体的未知配体.
- 阐明P2RY8信号在生殖中心组织和B细胞恶性瘤中的作用.
主要方法:
- 在生物样本和细胞上浮物中选P2RY8配体.
- 生物化学分化和质谱测量以识别新生物分子.
- 在体外和体内评估细胞迁移,信号和受体激活的功能性测试.
主要成果:
- 鉴定出S- 格拉尼尔- L- 氨酸 (GGG) 是一种在淋巴细胞组织中存在的强效P2RY8配体.
- GGG 抑制了生殖中心 B 细胞和毛囊 T 辅助细胞的化学因子介导迁移.
- 它的过度表达破坏了P2RY8介导的B细胞封闭.
结论:
- GGG是一种细胞间信号分子,通过控制B细胞迁移来组织生殖中心的反应.
- GGT5 建立了 GGG 梯度,调节了 B 细胞在淋巴组织中的局部化.
- GGG和P2RY8信号可能是B细胞恶性瘤和其他癌症的治疗点.
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