p120 catenin recruits cadherins to gamma-secretase and inhibits production of Abeta peptide
Journal of Biological Chemistry. 2009-01-01; 284(4): 1954-1961
DOI: 10.1074/jbc.m806250200
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Kouchi Z(1), Barthet G, Serban G, Georgakopoulos A, Shioi J, Robakis NK.
Author information:
(1)Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA.
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.