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Biochem Biophys Res Commun. 2006 Jul 7;345(3):951-8. Epub 2006 May 6.

Activity-dependent regulation of beta-catenin via epsilon-cleavage of N-cadherin.

Author information

1
Horizontal Medical Research Organization, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.

Abstract

N-cadherin is essential for excitatory synaptic contact in the hippocampus. Presenilin 1 (PS1) is located at sites of synaptic contact, forming a complex with N-cadherin and beta-catenin. Here, we report that human N-cadherin is cleaved by PS1/gamma-secretase in response to physiological concentration of glutamate (Glu) stimulation, yielding a fragment Ncad/CTF2. The expression of Ncad/CTF2 in neuronal cells led to its translocation to the nucleus, and caused a prominent enhancement of cytoplasmic and nuclear beta-catenin levels in a cell-cell contact dependent manner, via following mechanisms: 1, inhibition of beta-catenin phosphorylation; 2, transactivation of beta-catenin; and 3, inhibition of N-cadherin transcription, and finally enhanced beta-catenin nuclear signaling. Since the regulation of cellular beta-catenin level is essential for synaptic function, disruption in the cleavage of N-cadherin may be causally linked to the synaptic dysfunction associated with Alzheimer's disease (AD).

PMID:
16707106
DOI:
10.1016/j.bbrc.2006.04.157
[Indexed for MEDLINE]

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