A novel cross-talk between endothelin and ErbB receptors controlling glutamate transporter expression in astrocytes |
| |
Authors: | Glisic Darko Lehmann Claudia Figiel Maciej Ödemis Veysel Lindner Ricco Engele Jürgen |
| |
Institution: | Institute of Anatomy, University of Leipzig, Medical Faculty, Leipzig, Germany. |
| |
Abstract: | The 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. |
| |
Keywords: | astrocytes EGF endothelins GLT‐1/EAAT‐2 receptor internalization |
本文献已被 PubMed 等数据库收录! |
|