Jeong Wonyoung, Jho Eek-Hoon
Department of Life Science, University of Seoul, Seoul, South Korea.
Front Cell Dev Biol. 2021 Sep 13;9:714330. doi: 10.3389/fcell.2021.714330. eCollection 2021.
Wnt signaling plays crucial roles in development and tissue homeostasis, and its dysregulation leads to various diseases, notably cancer. Wnt/β-catenin signaling is initiated when the glycoprotein Wnt binds to and forms a ternary complex with the Frizzled and low-density lipoprotein receptor-related protein 5/6 (LRP5/6). Despite being identified as a Wnt co-receptor over 20 years ago, the molecular mechanisms governing how LRP6 senses Wnt and transduces downstream signaling cascades are still being deciphered. Due to its role as one of the main Wnt signaling components, the dysregulation or mutation of LRP6 is implicated in several diseases such as cancer, neurodegeneration, metabolic syndrome and skeletal disease. Herein, we will review how LRP6 is activated by Wnt stimulation and explore the various regulatory mechanisms involved. The participation of LRP6 in other signaling pathways will also be discussed. Finally, the relationship between LRP6 dysregulation and disease will be examined in detail.
Wnt信号通路在发育和组织稳态中发挥着关键作用，其失调会导致各种疾病，尤其是癌症。当糖蛋白Wnt与卷曲蛋白（Frizzled）以及低密度脂蛋白受体相关蛋白5/6（LRP5/6）结合并形成三元复合物时，Wnt/β-连环蛋白信号通路被激活。尽管LRP6在20多年前就被确定为Wnt共受体，但控制LRP6如何感知Wnt并转导下游信号级联反应的分子机制仍在被破解。由于LRP6作为主要的Wnt信号成分之一，其失调或突变与多种疾病有关，如癌症、神经退行性疾病、代谢综合征和骨骼疾病。在此，我们将综述LRP6如何被Wnt刺激激活，并探讨其中涉及的各种调节机制。还将讨论LRP6参与其他信号通路的情况。最后，将详细研究LRP6失调与疾病之间的关系。
