A novel cross‐talk between endothelin and ErbB receptors controlling glutamate transporter expression in astrocytes
A novel cross‐talk between endothelin and ErbB receptors controlling glutamate transporter expression in astrocytes
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内皮素和 ErbB 受体之间的新型串扰控制星形胶质细胞中谷氨酸转运蛋白的表达
DOI：
10.1111/j.1471-4159.2012.07819.x
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发表时间：
2012
影响因子：
4.7
通讯作者：
Engele J
中科院分区：
文献类型：
--
作者：
Glisic D;Lehmann C;Figiel M;Ödemis V;Lindner R;Engele J
神经化学杂志。（2012）122，844- 855.摘要内皮素和表皮生长因子（EGF）系统是控制反应性脑过程的中心，并且被认为通过内皮素诱导的表皮生长因子受体（EGFR）的反式激活部分地发挥这些任务。在此，我们表明，除了EGFR反式激活之外，内皮素阻止配体诱导的EGFR内化。我们揭示了内皮素通过促进“内化缺陷型”EGFR/ErB 2-异二聚体的形成或通过激活c-Abl激酶（EGFR内化的负调节因子）来消除EGFR的内化。我们进一步提供证据表明，这种串扰在星形胶质细胞谷氨酸转运的控制中是可操作的。具体而言，我们确定内皮素对主要星形胶质细胞谷氨酸转运子亚型（谷氨酸转运子1）的基础和EGF诱导表达的抑制作用是EGFR在细胞表面的内皮素依赖性保留的直接结果。我们的研究结果揭示了内皮素和表皮生长因子受体之间以前未知的相互作用，这可能对各种病理状况产生影响。
J. Neurochem.(2012)122, 844–855.AbstractThe endothelin and epidermal growth factor (EGF) systems are central to the control of reactive brain processes and are thought to partly exert these tasks by endothelin‐induced transactivation of the epidermal growth factor receptor (EGFR) Here we show that beyond EGFR transactivation, endothelins prevent the ligand‐induced internalization of the EGFR. We unravel that endothelins abrogate internalization of the EGFR by either promoting the formation of “internalization‐deficient” EGFR/ErB2‐heterodimers or by activating c‐Abl kinase, a negative regulator of EGFR internalization. We further provide evidence that this cross‐talk is operational in the control of astrocytic glutamate transport. Specifically, we establish that the inhibitory effects exerted by endothelins on basal as well as EGF‐induced expression of the major astroglial glutamate transporter subtype, glutamate transporter 1, are a direct consequence of the endothelin‐dependent retention of the EGFR at the cell surface. Together our findings unravel a previously unknown cross‐talk between endothelin and epidermal growth factor receptors, which may have implications for a variety of pathological conditions.
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