CXCR7 is an active component of SDF-1 signalling in astrocytes and Schwann cells
CXCR7 is an active component of SDF-1 signalling in astrocytes and Schwann cells
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DOI：
10.1242/jcs.062810
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发表时间：
2010-04-01
影响因子：
4
通讯作者：
Engele, Juergen
中科院分区：
文献类型：
--
作者：
Oedemis, Veysel;Boosmann, Karina;Engele, Juergen
另一种SDF-1（基质细胞衍生因子-1）受体CXCR 7被认为是细胞外SDF-1的清除剂或主要SDF-1受体CXCR 4的调节剂。然而，CXCR 7也直接影响各种肿瘤细胞类型的功能。在这里，我们证明了CXCR 7是星形胶质细胞和雪旺细胞中SDF-1信号传导的活性成分。培养的皮质星形胶质细胞和外周神经雪旺细胞表现出相当的总的和细胞表面的两种SDF-1受体的表达水平。用SDF-1刺激星形胶质细胞导致Erk 1/2、Akt和PKC zeta/lambda的暂时激活，但不导致p38和PKC α/β的暂时激活。雪旺细胞显示SDF-1诱导的Erk 1/2、Akt和p38活化，但不诱导PKC α/β和PKC ζ/λ活化。在CXCR 4缺陷小鼠的星形胶质细胞中，各自的信号传导模式仍然是完全可诱导的，但在RNAi耗尽星形胶质细胞CXCR 7后被废除。在Schwann细胞中，RNAi介导的CXCR 4或CXCR 7的耗竭沉默了SDF-1信号传导。CXCR 7拮抗剂CCX 754重现了星形胶质细胞受体耗竭实验的结果，但CXCR 4拮抗剂AMD 3100没有重现，两者都消除了星形胶质细胞SDF-1信号传导。进一步强调CXCR 7信号在神经胶质细胞中的功能重要性，我们表明SDF-1对两种神经胶质细胞类型的促有丝分裂作用在消耗CXCR 7后受损。
The alternative SDF-1 (stromal cell derived factor-1) receptor, CXCR7, has been suggested to act as either a scavenger of extracellular SDF-1 or a modulator of the primary SDF-1 receptor, CXCR4. CXCR7, however, also directly affects the function of various tumor-cell types. Here, we demonstrate that CXCR7 is an active component of SDF-1 signalling in astrocytes and Schwann cells. Cultured cortical astrocytes and peripheral nerve Schwann cells exhibit comparable total and cell-surface levels of expression of both SDF-1 receptors. Stimulation of astrocytes with SDF-1 resulted in the temporary activation of Erk1/2, Akt and PKC zeta/lambda, but not p38 and PKC alpha/beta. Schwann cells showed SDF-1-induced activation of Erk1/2, Akt and p38, but not PKC alpha/beta and PKC zeta/lambda. The respective signalling pattern remained fully inducible in astrocytes from CXCR4-deficient mice, but was abrogated following depletion of astrocytic CXCR7 by RNAi. In Schwann cells, RNAi-mediated depletion of either CXCR4 or CXCR7 silenced SDF-1 signalling. The findings of the astrocytic receptor-depletion experiments were reproduced by CXCR7 antagonist CCX754, but not by CXCR4 antagonist AMD3100, both of which abolished astrocytic SDF-1 signalling. Further underlining the functional importance of CXCR7 signalling in glial cells, we show that the mitogenic effects of SDF-1 on both glial cell types are impaired upon depleting CXCR7.