8月31日,，《生物化學期刊》（The Journal of Biological Chemistry）在線發(fā)表了中科院上海生命科學研究院生化與細胞所李林研究組的最新研究成果，揭示了NFAT蛋白調(diào)控經(jīng)典Wnt信號通路的分子機制,，及其在神經(jīng)祖細胞增殖和分化過程中的功能,。
Wnt信號通路是廣泛存在于多細胞真核生物中的一條高度保守的信號通路,，在胚胎發(fā)育過程中起到重要作用，例如促進神經(jīng)祖細胞的增殖,，抑制其分化,。在對Wnt信號通路的研究中，其他信號通路與Wnt信號通路之間的相互作用也成為近年來研究的熱點,。
博士研究生黃濤等人發(fā)現(xiàn),，NFAT這一鈣信號的重要下游分子在鈣信號的調(diào)節(jié)下，與Dvl這一經(jīng)典Wnt信號通路的重要分子存在相互作用,。在細胞核內(nèi),，NFAT通過與Dvl的相互作用，抑制Dvl與β-catenin的相互作用,，從而影響轉錄復合物（Dvl-β-catenin-TCF-c-Jun）的形成,，進而起到抑制經(jīng)典Wnt信號通路的作用。進一步的工作還發(fā)現(xiàn),，在雞胚神經(jīng)管發(fā)育的過程中,，NFAT通過對經(jīng)典Wnt信號的抑制，從而抑制神經(jīng)祖細胞的增殖,，促進神經(jīng)細胞的分化,。
該研究首次詳細闡明了NFAT對經(jīng)典Wnt信號產(chǎn)生抑制的分子機制，并揭示了NFAT在神經(jīng)祖細胞分化過程中的重要作用,。
該項工作與景乃禾研究組合作完成,，并得到了科技部、國家自然科學基金委,、中國科學院以及上海市科委的經(jīng)費支持,。(生物谷 Bioon.com)
doi:10.1074/jbc.P111.253401
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NFAT proteins repress canonical Wnt signaling via its interaction with Dvl and participate in regulating neural progenitor cell proliferation and differentiation
Tao Huang, Zhihui Xie, Jiyong Wang, Meng Li, Naihe Jing and Lin Li
The Ca2+ signaling pathway appears to regulate the processes of the early development through its antagonism of canonical Wnt/β-catenin signaling pathway. However, the underlying mechanism is still poorly understood. Here, we show that NFAT, a component of Ca2+ signaling, directly interacts with Dvl in a Ca2+-dependent manner. A dominant-negative form of NFAT rescued the inhibition of the Wnt/β-catenin pathway triggered by Ca2+ signal. NFAT functioned downstream of β-catenin without interfering with its stability, but influencing the interaction of β-catenin with Dvl by its competitively binding to Dvl. Furthermore, we demonstrate that NFAT is a regulator in the proliferation and differentiation of neural progenitor cells by modulating canonical Wnt/β-catenin signaling pathway in the neural tube of chick embryo. Our findings suggest that NFAT negatively regulates canonical Wnt/β-catenin signaling by binding to Dvl, thereby participating in vertebrate neurogenesis.
