Optogenetic Control of the Canonical Wnt Signaling Pathway During Xenopus laevis Embryonic Development.
Optogenetic Control of the Canonical Wnt Signaling Pathway During Xenopus laevis Embryonic Development.
复制标题
非洲爪蟾胚胎发育过程中典型Wnt信号通路的光遗传调控。
DOI：
10.1016/j.jmb.2021.167050
复制
发表时间：
2021-09-03
影响因子：
5.6
通讯作者：
Zhang K
中科院分区：
文献类型：
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作者：
Krishnamurthy VV;Hwang H;Fu J;Yang J;Zhang K
光遗传学利用光诱导蛋白质-蛋白质相互作用来精确控制信号传导活动的时间、定位和强度。这一新兴技术的精确空间和时间分辨率已被证明对胚胎发育的研究极具吸引力，胚胎发育是一个忠实地复制以从单细胞形成相同生物体的程序。我们之前已经进行了受体酪氨酸激酶的光遗传学激活的比较研究，其中我们发现基于细胞质到膜易位的光遗传学系统在激活活的非洲爪蟾胚胎中的受体酪氨酸激酶信号传导方面优于基于膜的二聚化策略。在这里，我们确定这种工程策略是否可以推广到其他涉及膜结合受体的信号通路。作为一个概念的证明，我们证明了低密度脂蛋白受体相关蛋白-6（LRP 6）的细胞质到膜的易位，经典Wnt通路的膜结合辅助受体，触发Wnt活性。LRP 6的光遗传激活导致非洲爪蟾胚胎发育中的轴复制，表明膜结合受体的胞质-膜易位可能是构建光遗传系统的一种可推广的策略。
Optogenetics uses light-inducible protein-protein interaction to precisely control the timing, localization, and intensity of signaling activity. The precise spatial and temporal resolution of this emerging technology has proven extremely attractive to the study of embryonic development, a program faithfully replicated to form the same organism from a single cell. We have previously performed a comparative study for optogenetic activation of receptor tyrosine kinases, where we found that the cytoplasm-to-membrane translocation-based optogenetic systems outperform the membrane-based dimerization strategy in activating the receptor tyrosine kinase signaling in live Xenopus embryos. Here, we determine if this engineering strategy can be generalized to other signaling pathways involving membrane-bound receptors. As a proof of concept, we demonstrate that the cytoplasm-to-membrane translocation of the low-density lipoprotein receptor-related protein-6 (LRP6), a membrane-bound coreceptor for the canonical Wnt pathway, triggers Wnt activity. Optogenetic activation of LRP6 leads to axis duplication in developing Xenopus embryos, indicating that the cytoplasm-to-membrane translocation of the membrane-bound receptor could be a generalizable strategy for the construction of optogenetic systems.