p120 catenin recruits cadherins to gamma-secretase and inhibits production of Abeta peptide.
J Biol Chem
; 284(4): 1954-61, 2009 Jan 23.
Article
em En
| MEDLINE
| ID: mdl-19008223
ABSTRACT
The gamma-secretase complex cleaves many transmembrane proteins, including amyloid precursor protein, EphB and ErbB tyrosine kinase receptors, Notch1 receptors, and adhesion factors. Presenilin 1, the catalytic subunit of gamma-secretase, associates with the cadherin/catenin cell-cell adhesion/communication system and promotes cadherin processing (Georgakopoulos, A., et al. (1999) Mol. Cell 4, 893-902; Marambaud, P., et al. (2002) EMBO J. 21, 1948-1956), but the mechanism by which gamma-secretase and cadherins associate is unclear. Here we report that p120 catenin (p120ctn), a component of the cadherin-catenin complex, recruits gamma-secretase to cadherins, thus stimulating their processing while inhibiting production of Abeta peptide and the amyloid precursor protein intracellular domain. This function of p120ctn depends on both p120ctn-cadherin and p120ctn-presenilin 1 binding, indicating that p120ctn is the central factor that bridges gamma-secretase and cadherin-catenin complexes. Our data show that p120ctn is a unique positive regulator of the gamma-secretase processing of cadherins and a negative regulator of the amyloid precursor protein processing. Furthermore, our data suggest that specific members of the gamma-secretase complex may be used to recruit different substrates and that distinct PS1 sequences are required for processing of APP and cadherins.
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Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
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Caderinas
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Moléculas de Adesão Celular
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Peptídeos beta-Amiloides
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Secretases da Proteína Precursora do Amiloide
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article