Familial Alzheimer's disease-associated mutations block translocation of full-length presenilin 1 to the nuclear envelope.
Neurosci Res
; 37(2): 101-11, 2000 Jun.
Article
em En
| MEDLINE
| ID: mdl-10867173
ABSTRACT
A polyclonal antibody, M5, to the hydrophilic loop domain of human presenilin 1 (PS1) was prepared. Western blot and immunoprecipitation analyses showed that M5 specifically recognized the processed C-terminal fragment, but not the full-length PS1. Epitope mapping analysis revealed that the essential sequence for recognition of the C-terminal fragment by M5 is DPEAQRR (302-308). The recognition of the C-terminal fragment by M5 in a processing-dependent manner was further confirmed by competitive enzyme-linked immunosorbent assay using the synthetic peptide L281 (281-311), which contains the putative processing site and the preceding amino acids to the site. Although L281 contains the epitope sequence for M5, the maximum inhibition was only 14%. Immunocytochemistry using M5 combined with hL312, which recognizes both full-length PS1 and the C-terminal fragment, allowed us to distinguish the localization of the processed C-terminal fragment from that of full-length PS1. Confocal microscopy demonstrated that the full-length form of wild-type PS1 is preferentially located in the nuclear envelope, while the processed C-terminal fragment is mainly present in the endoplasmic reticulum (ER). However, PS1 with familial Alzheimer's disease-associated mutations could not translocate to the nuclear envelope, and both the full-length and processed mutants were co-localized in the ER.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Alzheimer
/
Proteínas de Membrana
/
Mutação
/
Membrana Nuclear
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Neurosci Res
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Japão