Presenilin-1 influences processing of the acetylcholinesterase membrane anchor PRiMA
Presenilin-1 (PS1) is the catalytic component of the gamma-secretase complex. In this study, we explore if PS1 participates in the processing of the cholinergic acetylcholinesterase (AChE). The major AChE variant expressed in the brain is a tetramer (G(4)) bound to a proline-rich membrane anchor (PR...
| Autores: | , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2014 |
| País: | España |
| Institución: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repositorio: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p8913 |
| Acceso en línea: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=8913 http://hdl.handle.net/10261/103460 |
| Access Level: | acceso abierto |
| Palabra clave: | Alzheimer's disease gamma-Secretase Presenilin 1 Acetylcholinesterase PRiMA |
| Sumario: | Presenilin-1 (PS1) is the catalytic component of the gamma-secretase complex. In this study, we explore if PS1 participates in the processing of the cholinergic acetylcholinesterase (AChE). The major AChE variant expressed in the brain is a tetramer (G(4)) bound to a proline-rich membrane anchor (PRiMA). Overexpression of the transmembrane PRiMA protein in Chinese hamster ovary cells expressing AChE and treated with the gamma-secretase inhibitor N-[ N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester have enabled us to study whether, through its g-secretase activity, PS1 participates in the processing of PRiMA-linked AChE. gamma-Secretase inhibition led to a notable increase in the level of PRiMAlinked AChE, suggesting that gamma-secretase is involved in the cleavage of PRiMA. We demonstrate that cleavage of PRiMA by gamma-secretase results in a C-terminal PRiMA fragment. Immunofluorescence labeling allowed us to identify this PRiMA fragment in the nucleus. Moreover, we have determined changes in the proportion of the raft-residing AChE-PRiMA in a PS1 conditional knockout mouse. Our results are of interest as both enzymes have therapeutic relevance for Alzheimer's disease. (C) 2014 Elsevier Inc. All rights reserved. |
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