Institute of Biology, Department of Biochemistry, University of Hohenheim, 70599 Stuttgart, Germany.
Int J Mol Sci. 2022 Nov 24;23(23):14674. doi: 10.3390/ijms232314674.
Vertebrate and fly rhodopsins are prototypical GPCRs that have served for a long time as model systems for understanding GPCR signaling. Although all rhodopsins seem to become phosphorylated at their C-terminal region following activation by light, the role of this phosphorylation is not uniform. Two major functions of rhodopsin phosphorylation have been described: (1) inactivation of the activated rhodopsin either directly or by facilitating binding of arrestins in order to shut down the visual signaling cascade and thus eventually enabling a high-temporal resolution of the visual system. (2) Facilitating endocytosis of activated receptors via arrestin binding that in turn recruits clathrin to the membrane for clathrin-mediated endocytosis. In vertebrate rhodopsins the shutdown of the signaling cascade may be the main function of rhodopsin phosphorylation, as phosphorylation alone already quenches transducin activation and, in addition, strongly enhances arrestin binding. In the visual system rhodopsin phosphorylation is not needed for receptor inactivation. Its role here may rather lie in the recruitment of arrestin 1 and subsequent endocytosis of the activated receptor. In this review, we summarize investigations of fly rhodopsin phosphorylation spanning four decades and contextualize them with regard to the most recent insights from vertebrate phosphorylation barcode theory.
脊椎动物和蝇类视紫红质是典型的 G 蛋白偶联受体，长期以来一直作为理解 GPCR 信号转导的模型系统。尽管所有的视紫红质在被光线激活后似乎都会在其 C 末端区域发生磷酸化，但这种磷酸化的作用并不统一。视紫红质磷酸化有两个主要功能：（1）通过促进与阻滞蛋白的结合来直接或间接地使激活的视紫红质失活，从而关闭视觉信号级联，从而最终实现视觉系统的高时间分辨率。（2）通过与阻滞蛋白结合促进激活受体的内吞作用，进而将网格蛋白募集到质膜上进行网格蛋白介导的内吞作用。在脊椎动物视紫红质中，信号级联的关闭可能是视紫红质磷酸化的主要功能，因为磷酸化本身已经抑制了转导蛋白的激活，并且还强烈增强了阻滞蛋白的结合。在视觉系统中，受体失活不需要视紫红质磷酸化。它在这里的作用可能在于募集阻滞蛋白 1 并随后内吞激活的受体。在这篇综述中，我们总结了对蝇类视紫红质磷酸化的研究，跨越了四个十年，并将其与来自脊椎动物磷酸化条码理论的最新见解联系起来。
