9月出版的《细胞生物学杂志》(Journal of Cell biology) 报道了中科院上海生命科学研究院生物化学与细胞生物学研究所李林研究组的最新研究发现：一个参与Wnt 信号调节的新成员Caprin-2。
Wnt信号途径是多细胞真核生物中高度保守的一类信号传导途径。在动物体早期发育中，Wnt信号影响了体轴诱导、胚层建立、体节分化、组织或器官形成等一系列重要事件。在成体中，Wnt信号途径的异常激活，会引起许多生理缺陷，甚至诱发肿瘤。Wnt信号传递过程中，细胞膜上的共受体LRP5/6的磷酸化现象对于信号向细胞内传递是至关重要的。
在这项工作中，李林研究组的丁昱和席莹等发现了一个新的调节经典Wnt信号传递的蛋白质，Caprin-2。他们首先发现并证明了Caprin-2和LRP5/6在体内/体外有直接相互作用。过量表达Caprin-2或者降低内源Caprin-2会影响Wnt 相关报告基因活性和下游靶基因的表达，提示Caprin-2 可能作为正向调节子参与经典Wnt 信号转导途径。利用斑马鱼胚胎发育系统确认了Caprin-2 参与调节了Wnt信号，从而在Wnt信号转导途径/网络的构成上增添了新的认识。他们的进一步机制研究表明，Caprin-2 能够增强GSK3 介导的LRP5/6 的磷酸化，进而增强LRP5/6 与Axin 的相互作用，从而在经典Wnt信号转导过程中发挥功能。 （生物谷Bioon.com）
生物谷推荐原始出处：
The Journal of Cell Biology, Vol. 182, No. 5, 865-872 doi:10.1083/jcb.200803147
Caprin-2 enhances canonical Wnt signaling through regulating LRP5/6 phosphorylation
Yu Ding1, Ying Xi1, Ting Chen1, Ji-yong Wang1, Dong-lei Tao1, Zhi-Li Wu2, Yi-ping Li2, Chen Li3, Rong Zeng3, and Lin Li1
1 State Key Laboratory of Molecular Biology,
2 Laboratory of Molecular Cell Biology,
3 Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Correspondence to Lin Li: lli@sibs.ac.cn
The low-density lipoprotein receptor–related proteins 5 and 6 (LRP5/6) are coreceptors for Frizzled and transmit signals from the plasma membrane to the cytosol. However, the mechanism for LRP5/6 signal transmission remains undefined. Here, we identify cytoplasmic activation/proliferation-associated protein 2 (Caprin-2) as a LRP5/6-binding protein. Our data show that Caprin-2 stabilizes cytosolic β-catenin and enhances lymphoid enhancer-binding factor 1/T cell factor–dependent reporter gene activity as well as the expression of Wnt target genes in mammalian cells.Morpholino-mediated knockdown of Caprin-2 in zebrafish embryos inhibits Wnt/β-catenin signaling and results in a dorsalized phenotype. Moreover,Caprin-2 facilitates LRP5/6 phosphorylation by glycogen synthase kinase 3, and thus enhances the interaction between Axin and LRP5/6. Therefore,Caprin-2 promotes activation of the canonical Wnt signaling pathway by regulating LRP5/6 phosphorylation.
