HtrA1-dependent proteolysis of TGF-β controls both neuronal maturation and developmental survival
| Autor: | Séverine Launay, Denis Vivien, Cecilia Gabriel, Michael Ehrmann, Alfonso Baldi, Marie-Claude Potier, Mara Campioni, Luce Dauphinot, Eric Maubert, Fabian Docagne, Nathalie Lebeurrier, Annette Tennstaedt |
|---|---|
| Přispěvatelé: | Launay, S, Maubert, E, Lebeurrier, N, Tennstaedt, A, Campioni, M, Docagne, F, Gabriel, C, Ehrmann, M, Baldi, Alfonso, Vivien, D. |
| Rok vydání: | 2008 |
| Předmět: |
Cell Survival
Excitotoxicity Synaptogenesis Mice Transgenic Biology Serpin medicine.disease_cause Transforming Growth Factor beta1 Mice medicine Animals Molecular Biology Cells Cultured Neurons Serine Endopeptidases Wild type Brain Serine Protease HTRA1 High-Temperature Requirement A Serine Peptidase 1 Cell Biology Molecular biology Up-Regulation Cell biology Signal transduction Biologie Plasminogen activator Signal Transduction Transforming growth factor |
| Zdroj: | Cell Death & Differentiation. 15:1408-1416 |
| ISSN: | 1476-5403 1350-9047 |
| DOI: | 10.1038/cdd.2008.82 |
| Popis: | Transforming growth factor-beta (TGF-beta) signalling controls a number of cerebral functions and dysfunctions including synaptogenesis, amyloid-beta accumulation, apoptosis and excitotoxicity. Using cultured cortical neurons prepared from either wild type or transgenic mice overexpressing a TGF-beta-responsive luciferase reporter gene (SBE-Luc), we demonstrated a progressive loss of TGF-beta signalling during neuronal maturation and survival. Moreover, we showed that neurons exhibit increasing amounts of the serine protease HtrA1 (high temperature responsive antigen 1) and corresponding cleavage products during both in vitro neuronal maturation and brain development. In parallel of its ability to promote degradation of TGF-beta1, we demonstrated that blockage of the proteolytic activity of HtrA1 leads to a restoration of TGF-beta signalling, subsequent overexpression of the serpin type -1 plasminogen activator inhibitor (PAI-1) and neuronal death. Altogether, we propose that the balance between HtrA1 and TGF-beta could be one of the critical events controlling both neuronal maturation and developmental survival. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|