State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 100101 Beijing, China.
Biological Science Department, University of Chinese Academy of Sciences, 100049 Beijing, China.
Proc Natl Acad Sci U S A. 2018 Mar 6;115(10):E2254-E2263. doi: 10.1073/pnas.1717468115. Epub 2018 Feb 20.
Growing axons are exposed to various guidance cues en route to their targets, but the mechanisms that govern the response of growth cones to combinations of signals remain largely elusive. Here, we found that the sole Robo receptor, SAX-3, in functions as a coreceptor for Wnt/CWN-2 molecules. SAX-3 binds to Wnt/CWN-2 and facilitates the membrane recruitment of CWN-2. SAX-3 forms a complex with the Ror/CAM-1 receptor and its downstream effector Dsh/DSH-1, promoting signal transduction from Wnt to Dsh. functions in Wnt-responsive cells and the SAX-3 receptor is restricted to the side of the cell from which the neurite is extended. DSH-1 has a similar asymmetric distribution, which is disrupted by mutation. Taking these results together, we propose that Robo receptor can function as a Wnt coreceptor to regulate Wnt-mediated biological processes in vivo.
生长轴突在到达其靶标途中会暴露于各种导向线索中，但控制生长锥对信号组合做出反应的机制在很大程度上仍难以捉摸。在这里，我们发现 中的唯一 Robo 受体 SAX-3 可作为 Wnt/CWN-2 分子的共受体。SAX-3 与 Wnt/CWN-2 结合，并促进 CWN-2 的膜募集。SAX-3 与 Ror/CAM-1 受体及其下游效应物 Dsh/DSH-1 形成复合物，促进 Wnt 向 Dsh 的信号转导。 在 Wnt 反应性细胞中起作用，而 SAX-3 受体仅限于轴突延伸的细胞侧。DSH-1 具有类似的不对称分布，其被 突变破坏。综合这些结果，我们提出 Robo 受体可以作为 Wnt 共受体发挥作用，以调节体内的 Wnt 介导的生物学过程。
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