In animals, endocytosis of a seven-transmembrane GPCR is mediated by arrestins to propagate or arrest cytoplasmic G protein–mediated signaling, depending on the bias of the receptor or ligand, which determines how much one transduction pathway is used compared to another. In Arabidopsis thaliana, GPCRs are not required for G protein–coupled signaling because the heterotrimeric G protein complex spontaneously exchanges nucleotide. Instead, the seven-transmembrane protein AtRGS1 modulates G protein signaling through ligand-dependent endocytosis, which initiates derepression of signaling without the involvement of canonical arrestins. Here, we found that endocytosis of AtRGS1 initiated from two separate pools of plasma membrane: sterol-dependent domains and a clathrin-accessible neighborhood, each with a select set of discriminators, activators, and candidate arrestin-like adaptors. Ligand identity (either the pathogen-associated molecular pattern flg22 or the sugar glucose) determined the origin of AtRGS1 endocytosis. Different trafficking origins and trajectories led to different cellular outcomes. Thus, in this system, compartmentation with its associated signalosome architecture drives biased signaling.

在动物中，七跨膜 GPCR 的内吞作用是由抑制蛋白介导的，以传播或抑制细胞质 G 蛋白介导的信号传导，这取决于受体或配体的偏向性，这决定了一种转导通路与另一种相比的使用量。在拟南芥中，G蛋白偶联信号不需要GPCR，因为异源三聚体G蛋白复合物自发交换核苷酸。相反，七跨膜蛋白 AtRGS1 通过配体依赖性内吞作用调节 G 蛋白信号传导，这会在不涉及经典抑制蛋白的情况下启动信号传导的去抑制。在这里，我们发现 AtRGS1 的内吞作用从两个独立的质膜池开始：甾醇依赖性结构域和网格蛋白可接近的邻域，每个区域都有一组精选的鉴别器、激活剂和候选抑制蛋白样适配器。配体身份（病原体相关分子模式 flg22 或糖葡萄糖）决定了 AtRGS1 内吞作用的起源。不同的贩运起源和轨迹导致不同的细胞结果。因此，在这个系统中，