Vertebrate Wnt5a - At the crossroads of cellular signalling.
Vertebrate Wnt5a - At the crossroads of cellular signalling.
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DOI：
10.1016/j.semcdb.2021.10.002
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发表时间：
2021-10
影响因子：
7.3
通讯作者：
Sally Rogers;S. Scholpp
中科院分区：
文献类型：
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作者：
Sally Rogers;S. Scholpp
Wnt 信号传导是脊椎动物胚胎发生、分化、细胞运动、发育和成体组织稳态的重要途径。 Wnt 信号网络可以激活多个下游通路，例如 β-连环蛋白依赖性 TCF/LEF 转录、Wnt/平面细胞极性 (PCP) 通路和 Wnt/钙通路。 Wnt5a 是一种脊椎动物 Wnt 配体，通常与 Wnt/PCP 信号通路相关。 Wnt5a/PCP 信号传导通过与 Frizzled 及其辅助受体的受体复合物结合，启动 c-Jun N 末端激酶 (JNK) 信号级联以及 Rho 和 Rac GTPases、Rho-激酶 (ROCK) 的下游激活，在胚胎发生中发挥着重要作用。这种激活导致细胞极性、迁移以及随后的组织重排和器官形成所需的细胞骨架重塑。这篇综述将重点关注最近的工作，这些工作揭示了 Wnt5a 配体的新作用，从而揭示了一种新兴的更广泛的功能。这部分是由于我们对 Wnt/PCP 通路与 Wnt/β-连环蛋白通路和其他信号通路之间的串扰的了解不断加深，部分是由于 Wnt5a 的新型非典型受体的鉴定，证明了该配体具有更广泛的作用。
Wnt signalling is an essential pathway in embryogenesis, differentiation, cell motility, development, and adult tissue homeostasis in vertebrates. The Wnt signalling network can activate several downstream pathways such as the β-catenin-dependent TCF/LEF transcription, the Wnt/planar cell polarity (PCP) pathway, and the Wnt/Calcium pathway. Wnt5a is a vertebrate Wnt ligand that is most often associated with the Wnt/PCP signalling pathway. Wnt5a/PCP signalling has a well-described role in embryogenesis via binding to a receptor complex of Frizzled and its co-receptors to initiate downstream activation of the c-Jun N-terminal kinase (JNK) signalling cascade and the Rho and Rac GTPases, Rho-Kinase (ROCK). This activation results in the cytoskeletal remodelling required for cell polarity, migration, and subsequently, tissue re-arrangement and organ formation.This review will focus on more recent work that has revealed new roles for Wnt5a ligands and consequently, an emerging broader function. This is partly due to our growing understanding of the crosstalk between the Wnt/PCP pathway with both the Wnt/β-catenin pathway and other signalling pathways, and in part due to the identification of novel atypical receptors for Wnt5a that demonstrate a far broader role for this ligand.