The multiple signaling modalities of adhesion G protein-coupled receptor GPR126 in development.

The G protein-coupled receptor (GPCR) superfamily is the largest known receptor family in the human genome. Although the family of adhesion GPCRs comprises the second largest sub-family, their function is poorly understood. Here, we review the current knowledge about the adhesion GPCR family member GPR126. GPR126 possesses a signal peptide, a 7TM domain homologous to secretin-like GPCRs, a GPS motif and an extended N-terminus containing a CUB (Complement, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a hormone binding domain and 27 putative N-glycosylation sites. Knockdown and knockout experiments in zebrafish and mice have demonstrated that Gpr126 plays an essential role in neural, cardiac and ear development. In addition, genome-wide association studies have implicated variations at the GPR126 locus in obstructive pulmonary dysfunction, in scoliosis and as a determinant of trunk length and body height. Gpr126 appears to exert its function depending on the organ system via G protein- and/or N-terminus-dependent signaling. Here, we review the current knowledge about Gpr126, which, due to the variety of its functions and its multiple signaling modalities, provides a model adhesion GPCR to understand general functional concepts utilized by adhesion GPCRs.

G蛋白偶联受体（GPCR）超家族是人类基因组中已知的最大受体家族。尽管黏附类GPCR家族构成第二大亚家族，但对其功能了解甚少。在此，我们综述了关于黏附类GPCR家族成员GPR126的现有知识。GPR126具有一个信号肽、一个与促胰液素样GPCR同源的7次跨膜结构域、一个GPS基序以及一个包含CUB（补体、表皮生长因子样结构域、骨形态发生蛋白1）结构域、一个PTX（正五聚蛋白）结构域、一个激素结合结构域和27个假定的N -糖基化位点的延伸的N末端。在斑马鱼和小鼠中进行的基因敲低和基因敲除实验表明，Gpr126在神经、心脏和耳部发育中起着至关重要的作用。此外，全基因组关联研究表明，GPR126基因座的变异与阻塞性肺功能障碍、脊柱侧凸以及躯干长度和身高的决定因素有关。Gpr126似乎根据器官系统通过G蛋白依赖和/或N末端依赖的信号传导来发挥其功能。在此，我们综述了关于Gpr126的现有知识，由于其功能的多样性和多种信号传导方式，它为理解黏附类GPCR所利用的一般功能概念提供了一个黏附类GPCR的模型。