The heptahelical G protein-coupled receptors (GPCRs) belong to the largest family of cell surface signaling receptors encoded in the human genome. GPCRs signal to diverse extracellular stimuli and control a vast number of physiological responses, making this receptor class the target of nearly half the drugs currently in use. In addition to rapid desensitization, receptor trafficking is crucial for the temporal and spatial control of GPCR signaling. Sorting signals present in the intracytosolic domains of GPCRs regulate trafficking through the endosomal-lysosomal system. GPCR internalization is mediated by serine and threonine phosphorylation and arrestin binding. Short, linear peptide sequences including tyrosine- and dileucine-based motifs, and PDZ ligands that are recognized by distinct endocytic adaptor proteins also mediate internalization and endosomal sorting of GPCRs. We present new data from bioinformatic searches that reveal the presence of these types of sorting signals in the cytoplasmic tails of many known GPCRs. Several recent studies also indicate that the covalent modification of GPCRs with ubiquitin serves as a signal for internalization and lysosomal sorting, expanding the diversity of mechanisms that control trafficking of mammalian GPCRs.

中文翻译：

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G 蛋白偶联受体分选到核内体和溶酶体。

七螺旋 G 蛋白偶联受体 (GPCR) 属于人类基因组中编码的最大细胞表面信号受体家族。GPCRs 向不同的细胞外刺激发出信号并控制大量的生理反应，使这一类受体成为目前使用的近一半药物的靶标。除了快速脱敏，受体运输对于 GPCR 信号的时间和空间控制至关重要。GPCR 胞内结构域中存在的分选信号通过内体-溶酶体系统调节运输。GPCR 内化由丝氨酸和苏氨酸磷酸化和抑制蛋白结合介导。短的线性肽序列，包括基于酪氨酸和二亮氨酸的基序，被不同内吞衔接蛋白识别的 PDZ 配体也介导 GPCR 的内化和内体分选。我们提供了来自生物信息学搜索的新数据，这些数据揭示了许多已知 GPCR 的细胞质尾部中存在这些类型的分选信号。最近的几项研究还表明，用泛素对 GPCR 进行共价修饰可作为内化和溶酶体分选的信号，从而扩大了控制哺乳动物 GPCR 运输的机制的多样性。