Instituto de Neurociencias, Consejo Superior Universidad Miguel Hernández, Sant Joan d'Alacant 03550, Spain.
Neuron. 2011 Jan 13;69(1):77-90. doi: 10.1016/j.neuron.2010.12.006.
The chemokine Cxcl12 binds Cxcr4 and Cxcr7 receptors to control cell migration in multiple biological contexts, including brain development, leukocyte trafficking, and tumorigenesis. Both receptors are expressed in the CNS, but how they cooperate during migration has not been elucidated. Here, we used the migration of cortical interneurons as a model to study this process. We found that Cxcr4 and Cxcr7 are coexpressed in migrating interneurons, and that Cxcr7 is essential for chemokine signaling. Intriguingly, this process does not exclusively involve Cxcr7, but most critically the modulation of Cxcr4 function. Thus, Cxcr7 is necessary to regulate Cxcr4 protein levels, thereby adapting chemokine responsiveness in migrating cells. This demonstrates that a chemokine receptor modulates the function of another chemokine receptor by controlling the amount of protein that is made available for signaling at the cell surface.
趋化因子 Cxcl12 通过结合 Cxcr4 和 Cxcr7 受体来控制多种生物学背景下的细胞迁移，包括大脑发育、白细胞迁移和肿瘤发生。这两种受体都在中枢神经系统中表达，但它们在迁移过程中如何合作尚不清楚。在这里，我们使用皮质中间神经元的迁移作为模型来研究这个过程。我们发现 Cxcr4 和 Cxcr7 在迁移的中间神经元中共表达，并且 Cxcr7 对于趋化因子信号是必需的。有趣的是，这个过程并不完全涉及 Cxcr7，而是关键在于 Cxcr4 功能的调节。因此，Cxcr7 对于调节 Cxcr4 蛋白水平是必要的，从而使迁移细胞对趋化因子的反应性适应。这表明一种趋化因子受体通过控制细胞表面可用于信号转导的蛋白量来调节另一种趋化因子受体的功能。
