美国斯坦福大学医学院Thomas C. Südhof、K. Christopher Garcia等研究人员合作发现，RTN4/NoGo受体与BAI粘附-GPCR的结合调节神经元发育。该研究于2021年11月9日在线发表于国际一流学术期刊《细胞》。
研究人员表示，RTN4结合蛋白作为“NoGo”受体被广泛研究，但它们的生理相互作用和作用仍然难以捉摸。同样，BAI粘附-GPCR与许多活动相关，但它们的配体和功能仍不清楚。
使用无偏倚的方法，研究人员观察到了意想不到的趋同：RTN4受体是BAI粘附-GPCR的高亲和力配体。BAI的单个血小板反应蛋白1型重复（TSR）结构域以纳摩尔亲和力与所有三种RTN4受体亚型的富含亮氨酸重复结构域结合。在BAI1/RTN4受体复合物的1.65 Å晶体结构中，BAI TSR结构域中色氨酸的C-甘露糖基化和苏氨酸的O-岩藻糖基化创建了一个RTN4-受体/BAI界面，该界面由不寻常的糖缀合物形成，可实现高亲和力相互作用。
在人类神经元中，RTN4受体通过与神经胶质和神经元BAI的差异结合来调节树突分支化、轴突伸长和突触形成，从而控制神经网络活动。因此，BAI与RTN4/NoGo受体的结合代表了一个受体-配体轴，该轴由罕见的翻译后修饰启用，从而控制突触回路的发育。
附：英文原文
Title: RTN4/NoGo-receptor binding to BAI adhesion-GPCRs regulates neuronal development
Author: Jie Wang, Yi Miao, Rebecca Wicklein, Zijun Sun, Jinzhao Wang, Kevin M. Jude, Ricardo A. Fernandes, Sean A. Merrill, Marius Wernig, K. Christopher Garcia, Thomas C. Südhof
Issue&Volume: 2021-11-09
Abstract: RTN4-binding proteins were widely studied as “NoGo” receptors, but their physiologicalinteractors and roles remain elusive. Similarly, BAI adhesion-GPCRs were associatedwith numerous activities, but their ligands and functions remain unclear. Using unbiasedapproaches, we observed an unexpected convergence: RTN4 receptors are high-affinityligands for BAI adhesion-GPCRs. A single thrombospondin type 1-repeat (TSR) domainof BAIs binds to the leucine-rich repeat domain of all three RTN4-receptor isoformswith nanomolar affinity. In the 1.65 crystal structure of the BAI1/RTN4-receptorcomplex, C-mannosylation of tryptophan and O-fucosylation of threonine in the BAITSR-domains creates a RTN4-receptor/BAI interface shaped by unusual glycoconjugatesthat enables high-affinity interactions. In human neurons, RTN4 receptors regulatedendritic arborization, axonal elongation, and synapse formation by differential bindingto glial versus neuronal BAIs, thereby controlling neural network activity. Thus,BAI binding to RTN4/NoGo receptors represents a receptor-ligand axis that, enabledby rare post-translational modifications, controls development of synaptic circuits.
DOI: 10.1016/j.cell.2021.10.016
Source: https://www.cell.com/cell/fulltext/S0092-8674(21)01232-0