Presenilin 1 and presenilin 2 have differential effects on the stability and maturation of nicastrin in Mammalian brain.
J Biol Chem
; 278(22): 19974-9, 2003 May 30.
Article
em En
| MEDLINE
| ID: mdl-12646573
ABSTRACT
The presenilins and nicastrin form high molecular mass, multimeric protein complexes involved in the intramembranous proteolysis of several proteins. Post-translational glycosylation and trafficking of nicastrin is necessary for the activity of these complexes. We report here that although there are differences in the post-translational processing of nicastrin in neurons and glia, both of the presenilins are required for the physiological post-translational modification and for the correct subcellular distribution of nicastrin. Absence of presenilin 1 (PS1) is associated with dramatic reductions in the level of mature glycosylated nicastrin and with redistribution of nicastrin away from the cell surface. In contrast, absence of presenilin 2 (PS2) is associated with only modest reductions in the levels of immature nicastrin. It is notable that these differential effects parallel the differential effects of null mutations in PS1 and PS2 on APP and Notch processing. Our data therefore suggest that the differential interactions of PS1 and PS2 with nicastrin reflect different functions for the PS1 and PS2 complexes.
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Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Glicoproteínas de Membrana
/
Proteínas de Membrana
Limite:
Animals
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Canadá