| First Author | Shishido Y | Year | 2006 |
| Journal | Biochem Biophys Res Commun | Volume | 348 |
| Issue | 3 | Pages | 963-70 |
| PubMed ID | 16901467 | Mgi Jnum | J:111964 |
| Mgi Id | MGI:3655301 | Doi | 10.1016/j.bbrc.2006.07.129 |
| Citation | Shishido Y, et al. (2006) Activity-dependent shedding of heparin-binding EGF-like growth factor in brain neurons. Biochem Biophys Res Commun 348(3):963-70 |
| abstractText | Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is initially produced as a membrane-anchored precursor (pro-HB-EGF) and subsequently liberated from the cell membrane through ectodomain shedding. Here, we characterized the molecular regulation of pro-HB-EGF shedding in the central nervous system. Cultured neocortical or hippocampal neurons were transfected with the alkaline-phosphatase-tagged pro-HB-EGF gene and stimulated with various neurotransmitters. Both kainate and N-methyl-D-aspartate, but not agonists for metabotropic glutamate receptors, promoted pro-HB-EGF shedding and HB-EGF release, which were attenuated by an exocytosis blocker and metalloproteinase inhibitors. In the brain of transgenic mice over-expressing human pro-HB-EGF, kainate-induced seizure activity decreased content of pro-HB-EGF-like immunoreactivity and conversely increased levels of soluble HB-EGF. There was concomitant phosphorylation of EGF receptors (ErbB1) following seizures, suggesting that seizure activities liberated HB-EGF and activated neighboring ErbB1 receptors. Therefore, we propose that glutamatergic neurotransmission in the central nervous system plays a crucial role in regulating ectodomain shedding of pro-HB-EGF. |
