NMDA-receptor activation induces calpain-mediated beta-catenin cleavages for triggering gene expression
- PMID: 17270735
- DOI: 10.1016/j.neuron.2007.01.016
NMDA-receptor activation induces calpain-mediated beta-catenin cleavages for triggering gene expression
Abstract
The canonical Wnt-beta-catenin signaling pathway is important for a variety of developmental phenomena as well as for carcinogenesis. Here, we show that, in hippocampal neurons, NMDA-receptor-dependent activation of calpain induced the cleavage of beta-catenin at the N terminus, generating stable, truncated forms. These beta-catenin fragments accumulated in the nucleus and induced Tcf/Lef-dependent gene transcription. We identified Fosl1, one of the immediate-early genes, as a target of this signaling pathway. In addition, exploratory behavior by mice resulted in a similar cleavage of beta-catenin, as well as activation of the Tcf signaling pathway, in hippocampal neurons. Both beta-catenin cleavage and Tcf-dependent gene transcription were suppressed by calpain inhibitors. These findings reveal another pathway for beta-catenin-dependent signaling, in addition to the canonical Wnt-beta-catenin pathway, and suggest that this other pathway could play an important role in activity-dependent gene expression.
Comment in
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Picking up the pieces: the roles of functional remnants of calpain-mediated proteolysis.Neuron. 2007 Feb 1;53(3):317-9. doi: 10.1016/j.neuron.2007.01.014. Neuron. 2007. PMID: 17270728
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