T cell chemotaxis to lysophosphatidylcholine through the G2A receptor
T cell chemotaxis to lysophosphatidylcholine through the G2A receptor
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DOI：
10.1073/pnas.2536801100
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发表时间：
2004-01-06
影响因子：
11.1
通讯作者：
Witte, ON
中科院分区：
文献类型：
--
作者：
Radu, CG;Yang, LV;Witte, ON
G2 A是主要在淋巴细胞和巨噬细胞中表达的免疫调节性G蛋白偶联受体。异位过表达研究表明G2 A是生物活性溶血磷脂、溶血磷脂酰胆碱（LPC）的受体。然而，LPC-G2 A相互作用在受体表达的生理水平上的功能后果，以及在与其免疫作用相关的细胞背景下，仍然在很大程度上是未知的。在这里，我们显示受损的趋化性LPC的T淋巴细胞系，其中G2 A的表达是长期下调的RNA干扰技术。通过受体表达的生理水平的重建来拯救这种表型进一步支持LPC-G2 A相互作用和细胞运动性之间的功能性联系。G2 A在T淋巴细胞系中的过表达显著增强了对LPC的趋化性。它还修改了向LPC相关分子溶血磷脂酸的迁移，表明G2 A和内源性溶血磷脂酸受体之间可能存在串扰。G2 A在LPC介导的细胞迁移中的作用可能与小鼠中这种G蛋白偶联受体的遗传失活相关的自身免疫综合征有关。这里描述的实验系统可以是有用的理解LPC识别G2 A的结构要求和信号转导途径调节的配体受体对。
G2A is an immunoregulatory G protein-coupled receptor predominantly expressed in lymphocytes and macrophages. Ectopic overexpression 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 reconstitution 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.