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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >T cell chemotaxis to lysophosphatidylcholine through the G2A receptor
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T cell chemotaxis to lysophosphatidylcholine through the G2A receptor

机译：T细胞通过G2A受体趋化至溶血磷脂酰胆碱

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摘要

G2A is an immunoregulatory G protein-coupled receptor predominantly expressed in lymphocytes and macrophages. Ectopic over-expression studies have implicated G2A as a receptor for the bioactive lysophospholipid, lysophosphatidylcholine (LPC). However, the functional consequences of LPC-G2A interaction at physiological levels of receptor expression, and in a cellular context relevant to its immunological role, remain largely unknown. Here, we show impaired chemotaxis to LPC of a T lymphoid cell line in which G2A expression was chronically down-regulated by RNA interference technology. Rescuing this phenotype by reconstitu-tion of the physiological level of receptor expression further supports a functional connection between LPC-G2A interaction and cellular motility. Overexpression of G2A in the T lymphoid cell line significantly enhanced chemotaxis to LPC. It also modified migration toward the LPC-related molecule, lysophosphatidic acid, indicating the possibility of crosstalk between G2A and endogenous lysophosphatidic acid receptors. The role of G2A in LPC-mediated cell migration may be relevant to the autoimmune syndrome associated with genetic inactivation of this G protein-coupled receptor in mice. The experimental system described here can be useful for understanding the structural requirements for LPC recognition by G2A and the signaling pathways regulated by this ligand-receptor pair.
机译：G2A是主要在淋巴细胞和巨噬细胞中表达的一种免疫调节性G蛋白偶联受体。异位过表达研究表明G2A是生物活性溶血磷脂，溶血磷脂酰胆碱（LPC）的受体。然而，LPC-G2A相互作用在受体表达的生理水平以及与它的免疫学作用有关的细胞环境中的功能后果仍然是未知的。在这里，我们显示出T淋巴细胞样细胞系对LPC的趋化性受损，其中G2A表达被RNA干扰技术长期下调。通过重构受体表达的生理水平来挽救该表型，进一步支持了LPC-G2A相互作用与细胞运动性之间的功能联系。 T淋巴样细胞系中G2A的过表达显着增强了对LPC的趋化性。它还修饰了向LPC相关分子溶血磷脂酸的迁移，表明G2A与内源溶血磷脂酸受体之间可能发生串扰。 G2A在LPC介导的细胞迁移中的作用可能与这种G蛋白偶联受体在小鼠中的基因失活有关的自身免疫综合症有关。此处描述的实验系统对于理解G2A对LPC识别的结构要求以及由该配体-受体对调节的信号通路可能有用。

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