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Calsenilin regulates presenilin γ-secretase-mediated N-cadherin &epsilon-cleavage and β-catenin signaling.
- Source :
- FASEB Journal; Dec2011, Vol. 25 Issue 12, p4174-4183, 10p
- Publication Year :
- 2011
-
Abstract
- Presenilin 1 (PS1) is a component of the γ-secretase complex that cleaves a variety of type I membrane proteins, including the β-amyloid precursor protein (β-APP), Notch, and neuronal (N)- and epithelial (E)-cadherins. N-cadherin is an essential adhesion molecule that forms a complex with, and is cleaved by, PS1/γ-secretase and β-catenin in the plasma membrane. The purpose of this study was to determine whether calsenilin, a presenilin-interacting protein, has a functional role in PS1/γ-secretase-mediated N-cadherin ε-cleavage using Western blot analysis, RT-PCR, immunoprecipitation, subcellular fractionation, biotinylation, and a luciferase reporter assay in SH-SY5Y neuroblastoma cells. Here, we demonstrate that the expression of calsenilin leads to a disruption of PS1/γ-secretase-mediated ε-cleavage of N-cadherin, which results in the significant accumulation of N-cadherin C-terminal fragment 1 (Ncad/CTF1), the reduction of cytoplasmic Ncad/CTF2 release, and a deceleration of PS1-CTF delivery to the cell surface. Interestingly, we also found that the expression of calsenilin is associated with the redistribution of β-catenin from the cell surface to a cytoplasmic pool, as well as with the negative regulation of genes that are targets of T-cell factor/β-catenin nuclear signaling. Taken together, our findings suggest that calsenilin is a novel negative regulator of N-cadherin processing that plays an important role in β-catenin signaling. [ABSTRACT FROM AUTHOR]
- Subjects :
- PRESENILINS
MEMBRANE proteins
PROTEINS
CADHERINS
GLYCOPROTEINS
Subjects
Details
- Language :
- English
- ISSN :
- 08926638
- Volume :
- 25
- Issue :
- 12
- Database :
- Complementary Index
- Journal :
- FASEB Journal
- Publication Type :
- Academic Journal
- Accession number :
- 70184852
- Full Text :
- https://doi.org/10.1096/fj.11-185926