NMDA-receptor activation induces calpain-mediated β-catenin cleavages for triggering gene expression

被引:121
作者
Abe, Kentaro
Takeichi, Masatoshi [1 ]
机构
[1] Kyoto Univ, Grad Sch Biostudies, Sakyo Ku, Kyoto 6068502, Japan
[2] RIKEN, Ctr Dev Biol, Chuo Ku, Kobe, Hyogo 6500047, Japan
基金
日本学术振兴会;
关键词
D O I
10.1016/j.neuron.2007.01.016
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 immediateearly 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-catenindependent 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.
引用
收藏
页码:387 / 397
页数:11
相关论文
共 54 条
[31]   Noncanonical Wnt signaling and neural polarity [J].
Montcouquiol, Mireille ;
Crenshaw, E. Bryan, III ;
Kelley, Matthew W. .
ANNUAL REVIEW OF NEUROSCIENCE, 2006, 29 :363-386
[32]   WNT and β-catenin signalling:: Diseases and therapies [J].
Moon, RT ;
Kohn, AD ;
De Ferrari, GV ;
Kaykas, A .
NATURE REVIEWS GENETICS, 2004, 5 (09) :689-699
[33]   The role of cell adhesion molecules in synaptic plasticity and memory [J].
Murase, S ;
Schuman, EM .
CURRENT OPINION IN CELL BIOLOGY, 1999, 11 (05) :549-553
[34]   Depolarization drives β-catenin into neuronal spines promoting changes in synaptic structure and function [J].
Murase, S ;
Mosser, E ;
Schuman, EM .
NEURON, 2002, 35 (01) :91-105
[35]   NMDA receptors, place cells and hippocampal spatial memory [J].
Nakazawa, K ;
McHugh, TJ ;
Wilson, MA ;
Tonegawa, S .
NATURE REVIEWS NEUROSCIENCE, 2004, 5 (05) :361-372
[36]   Calpain mediates eukaryotic initiation factor 4G degradation during global brain ischemia [J].
Neumar, RW ;
DeGracia, DJ ;
Konkoly, LL ;
Khoury, JI ;
White, BC ;
Krause, GS .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1998, 18 (08) :876-881
[37]  
NUSSE R, 2006, WNT HOMEPAGE
[38]   Cadherin activity is required for activity-induced spine remodeling [J].
Okamura, K ;
Tanaka, H ;
Yagita, Y ;
Saekl, Y ;
Taguchi, A ;
Hiraoka, Y ;
Zeng, LH ;
Colman, DR ;
Miki, N .
JOURNAL OF CELL BIOLOGY, 2004, 167 (05) :961-972
[39]  
Polakis P, 2000, GENE DEV, V14, P1837
[40]   SRF mediates activity-induced gene expression and synaptic plasticity but not neuronal viability [J].
Ramanan, N ;
Shen, Y ;
Sarsfield, S ;
Lemberger, T ;
Schütz, G ;
Linden, DJ ;
Ginty, DD .
NATURE NEUROSCIENCE, 2005, 8 (06) :759-767