Abe Kentaro, Takeichi Masatoshi
Graduate School of Biostudies, Kyoto University, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan.
Neuron. 2007 Feb 1;53(3):387-97. doi: 10.1016/j.neuron.2007.01.016.
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.
经典的Wnt-β-连环蛋白信号通路对多种发育现象以及肿瘤发生都很重要。在此，我们表明，在海马神经元中，钙蛋白酶依赖NMDA受体的激活诱导了β-连环蛋白在N端的切割，产生稳定的截短形式。这些β-连环蛋白片段在细胞核中积累并诱导Tcf/Lef依赖的基因转录。我们确定即刻早期基因之一的Fosl1是该信号通路的一个靶点。此外，小鼠的探索行为导致海马神经元中β-连环蛋白发生类似的切割，以及Tcf信号通路的激活。钙蛋白酶抑制剂可抑制β-连环蛋白的切割和Tcf依赖的基因转录。这些发现揭示了除经典Wnt-β-连环蛋白通路外，另一条β-连环蛋白依赖的信号通路，并表明这条其他通路可能在活动依赖的基因表达中发挥重要作用。
