9月出版的《細(xì)胞生物學(xué)雜志》(Journal of Cell biology) 報(bào)道了中科院上海生命科學(xué)研究院生物化學(xué)與細(xì)胞生物學(xué)研究所李林研究組的最新研究發(fā)現(xiàn)：一個(gè)參與Wnt 信號(hào)調(diào)節(jié)的新成員Caprin-2。
Wnt信號(hào)途徑是多細(xì)胞真核生物中高度保守的一類信號(hào)傳導(dǎo)途徑,。在動(dòng)物體早期發(fā)育中,，Wnt信號(hào)影響了體軸誘導(dǎo)、胚層建立,、體節(jié)分化,、組織或器官形成等一系列重要事件。在成體中,，Wnt信號(hào)途徑的異常激活,，會(huì)引起許多生理缺陷，甚至誘發(fā)腫瘤,。Wnt信號(hào)傳遞過(guò)程中,，細(xì)胞膜上的共受體LRP5/6的磷酸化現(xiàn)象對(duì)于信號(hào)向細(xì)胞內(nèi)傳遞是至關(guān)重要的。
在這項(xiàng)工作中,，李林研究組的丁昱和席瑩等發(fā)現(xiàn)了一個(gè)新的調(diào)節(jié)經(jīng)典Wnt信號(hào)傳遞的蛋白質(zhì),，Caprin-2。他們首先發(fā)現(xiàn)并證明了Caprin-2和LRP5/6在體內(nèi)/體外有直接相互作用,。過(guò)量表達(dá)Caprin-2或者降低內(nèi)源Caprin-2會(huì)影響Wnt 相關(guān)報(bào)告基因活性和下游靶基因的表達(dá),，提示Caprin-2 可能作為正向調(diào)節(jié)子參與經(jīng)典Wnt 信號(hào)轉(zhuǎn)導(dǎo)途徑。利用斑馬魚胚胎發(fā)育系統(tǒng)確認(rèn)了Caprin-2 參與調(diào)節(jié)了Wnt信號(hào),，從而在Wnt信號(hào)轉(zhuǎn)導(dǎo)途徑/網(wǎng)絡(luò)的構(gòu)成上增添了新的認(rèn)識(shí),。他們的進(jìn)一步機(jī)制研究表明,，Caprin-2 能夠增強(qiáng)GSK3 介導(dǎo)的LRP5/6 的磷酸化，進(jìn)而增強(qiáng)LRP5/6 與Axin 的相互作用,，從而在經(jīng)典Wnt信號(hào)轉(zhuǎn)導(dǎo)過(guò)程中發(fā)揮功能,。 （生物谷Bioon.com）
生物谷推薦原始出處：
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: [email protected]
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.
