Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University.
Biol Pharm Bull. 2024;47(10):1600-1609. doi: 10.1248/bpb.b24-00571.
Because G protein coupled receptors (GPCRs) represent the largest family of drug targets in clinical trials, GPCR signaling cascades are closely related to various physiological phenomena, attracting significant attention in pharmaceutical science. Opsins (also known as animal rhodopsins) are photoreceptive proteins containing retinal as a chromophore, which function as GPCRs and underlie the molecular basis of photoreception in animals. Recently, opsins have been progressively applied in an innovative technology called optogenetics to regulate biological activities using light. A wide variety of opsins have been identified in metazoans and characterized at the molecular and physiological levels, providing a foundation for their optogenetic applications. In this review, I briefly introduce the diversity of opsins in terms of their molecular functions, including G protein selectivity and photoreaction properties. This diversity provides a significant advantage for optically manipulating a wide variety of GPCR signaling cascades with high temporal resolution. Additionally, I discuss the rich array of opsin-based optogenetic tools used to control various physiological processes and their potential as therapeutic tools for vision restoration. Based on the introduction, I expect that the optogenetic approach will offer powerful tools to provide valuable insights into the molecular mechanisms of various physiological phenomena and next-generation treatment options for diseases beyond the capacity of traditional drugs.
由于 G 蛋白偶联受体(GPCRs)是临床试验中最大的药物靶点家族,因此 GPCR 信号级联与各种生理现象密切相关,在药物科学中引起了极大关注。视蛋白(也称为动物视紫红质)是含有视黄醛作为生色团的感光蛋白,作为 GPCR 起作用,是动物光感受的分子基础。最近,视蛋白已逐渐应用于一种名为光遗传学的创新技术中,通过光来调节生物活性。在后生动物中已经鉴定出了各种各样的视蛋白,并在分子和生理水平上进行了表征,为其光遗传学应用提供了基础。在这篇综述中,我简要介绍了视蛋白在分子功能方面的多样性,包括 G 蛋白选择性和光反应特性。这种多样性为高时间分辨率地用光操纵各种 GPCR 信号级联提供了显著优势。此外,我还讨论了基于视蛋白的丰富的光遗传学工具,用于控制各种生理过程,以及它们作为视力恢复治疗工具的潜力。基于介绍,我预计光遗传学方法将提供强大的工具,为各种生理现象的分子机制提供有价值的见解,并为传统药物无法治疗的疾病提供下一代治疗选择。