Photic injury promotes cleavage of p75NTR by TACE and nuclear trafficking of the p75 intracellular domain
| Autor: | Zhaohui Wang, Collier Robert J, Rouel S. Roque, Roy A. Black, Bhooma Srinivasan, Philip A. Barker, Anne Marie Brun-Zinkernagel, Stuart J. Frank |
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| Rok vydání: | 2007 |
| Předmět: |
Intracellular Fluid
Active Transport Cell Nucleus Apoptosis Mice Transgenic ADAM17 Protein Biology Cleavage (embryo) Receptor Nerve Growth Factor Retina Cell Line Rats Sprague-Dawley Mice Cellular and Molecular Neuroscience Extracellular Disintegrin Animals Photoreceptor Cells Secretion Metalloprotease inhibitor Molecular Biology Cell Nucleus Metalloproteinase Cell Biology Molecular biology Protein Structure Tertiary Rats Cell biology ADAM Proteins Gene Expression Regulation Metalloproteases biology.protein Tumor necrosis factor alpha sense organs Photic Stimulation |
| Zdroj: | Molecular and Cellular Neuroscience. 36:449-461 |
| ISSN: | 1044-7431 |
| Popis: | The p75 neurotrophin receptor (p75NTR) is a member of the tumor necrosis factor receptor superfamily that paradoxically mediates neuronal survival and differentiation or apoptotic cell death. Cleavage of p75NTR by a constitutively active metalloprotease could result in shedding of its extracellular domain (p75ECD) and generation of a pro-apoptotic intracellular domain (p75ICD). In this study, we established that exposure of a transgenic mouse photoreceptor cell line to intense light upregulated the expression of p75NTR and of the disintegrin metalloprotease tumor necrosis factor-converting enzyme (TACE) and resulted in apoptotic cell death. Light damage promoted TACE cleavage of p75NTR resulting in shedding of the soluble p75ECD and nuclear translocation of the p75ICD. Overexpression of TACE and p75NTR-induced p75NTR cleavage and secretion of p75ECD, but not nuclear transport of p75ICD. Light-induced cleavage of p75NTR, nuclear localization of p75ICD, and apoptosis were inhibited by IC-3, a metalloprotease inhibitor. Increased levels of p75NTR and TACE were observed in photoreceptor cells of animals with photic injury. Our findings support a role for TACE in the proteolytic cleavage of p75NTR and light-induced apoptosis. |
| Databáze: | OpenAIRE |
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