BIN1 regulates BACE1 intracellular trafficking and amyloid-ß production.
Hum Mol Genet
; 25(14): 2948-2958, 2016 07 15.
Article
en En
| MEDLINE
| ID: mdl-27179792
ABSTRACT
BIN1 is a genetic risk factor of late-onset Alzheimer disease (AD), which was identified in multiple genome-wide association studies. BIN1 is a member of the amphiphysin family of proteins, and contains N-terminal Bin-Amphiphysin-Rvs and C-terminal Src homology 3 domains. BIN1 is widely expressed in the mouse and human brains, and has been reported to function in the endocytosis and the endosomal sorting of membrane proteins. BACE1 is a type 1 transmembrane aspartyl protease expressed predominantly in neurons of the brain and responsible for the production of amyloid-ß peptide (Aß). Here we report that the depletion of BIN1 increases cellular BACE1 levels through impaired endosomal trafficking and reduces BACE1 lysosomal degradation, resulting in increased Aß production. Our findings provide a mechanistic role of BIN1 in the pathogenesis of AD as a novel genetic regulator of BACE1 levels and Aß production.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Nucleares
/
Péptidos beta-Amiloides
/
Ácido Aspártico Endopeptidasas
/
Proteínas Supresoras de Tumor
/
Proteínas Adaptadoras Transductoras de Señales
/
Secretasas de la Proteína Precursora del Amiloide
/
Enfermedad de Alzheimer
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Hum Mol Genet
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2016
Tipo del documento:
Article