Presenilin mutations associated with Alzheimer disease cause defective intracellular trafficking of beta-catenin, a component of the presenilin protein complex.
Nat Med
; 5(2): 164-9, 1999 Feb.
Article
en En
| MEDLINE
| ID: mdl-9930863
ABSTRACT
The presenilin proteins are components of high-molecular-weight protein complexes in the endoplasmic reticulum and Golgi apparatus that also contain beta-catenin. We report here that presenilin mutations associated with familial Alzheimer disease (but not the non-pathogenic Glu318Gly polymorphism) alter the intracellular trafficking of beta-catenin after activation of the Wnt/beta-catenin signal transduction pathway. As with their effect on betaAPP processing, the effect of PS1 mutations on trafficking of beta-catenin arises from a dominant 'gain of aberrant function' activity. These results indicate that mistrafficking of selected presenilin ligands is a candidate mechanism for the genesis of Alzheimer disease associated with presenilin mutations, and that dysfunction in the presenilin-beta-catenin protein complexes is central to this process.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transactivadores
/
Proteínas del Citoesqueleto
/
Enfermedad de Alzheimer
/
Proteínas de la Membrana
/
Mutación
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Nat Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
MEDICINA
Año:
1999
Tipo del documento:
Article
País de afiliación:
Canadá