The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes
The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes
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DOI：
10.1074/jbc.m508234200
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发表时间：
2005-10-21
影响因子：
4.8
通讯作者：
Bachelerie, F
中科院分区：
文献类型：
--
作者：
Balabanian, K;Lagane, B;Bachelerie, F
系统发育和染色体定位相结合的研究表明，孤儿受体 RDC1 与 CXC 趋化因子受体相关。 RDC1为有限数量的人类免疫缺陷病毒（HIV）分离株提供共受体功能，特别是对于使用CXCR4的HIV-2 ROD毒株。在这里，我们展示了 CXCL12（CXCR4 唯一已知的天然配体）与 RDC1 结合并通过 RDC1 发出信号。我们证明RDC1在T淋巴细胞中表达，并且CXCL12促进的趋化性被抗RDC1单克隆抗体抑制。同时阻断 RDC1 和 CXCR4 对 CXCL12 诱导的 T 细胞迁移产生附加抑制作用。此外，我们提供的证据表明 CXCL12 与 RDC1 的相互作用是特异性的、可饱和的且具有高亲和力（表观 K-D = 0.4 nM）。在表达 RDC1 的 CXCR4 阴性细胞中，CXCL12 通过 RDC1 促进受体的内化和趋化信号。总的来说，我们的数据表明 RDC1（我们建议将其重命名为 CXCR7）是 CXCL12 的受体。
Combined phylogenetic and chromosomal location studies suggest that the orphan receptor RDC1 is related to CXC chemokine receptors. RDC1 provides a co- receptor function for a restricted number of human immunodeficiency virus ( HIV) isolates, in particular for the CXCR4- using HIV- 2 ROD strain. Here we show that CXCL12, the only known natural ligand for CXCR4, binds to and signals through RDC1. We demonstrate that RDC1 is expressed in T lymphocytes and that CXCL12- promoted chemotaxis is inhibited by an anti- RDC1 monoclonal antibody. Concomitant blockade of RDC1 and CXCR4 produced additive inhibitory effects in CXCL12-induced T cell migration. Furthermore, we provide evidence that interaction of CXCL12 with RDC1 is specific, saturable, and of high affinity ( apparent K-D = 0.4 nM). In CXCR4- negative cells expressing RDC1, CXCL12 promotes internalization of the receptor and chemotactic signals through RDC1. Collectively, our data indicate that RDC1, which we propose to rename as CXCR7, is a receptor for CXCL12.