Molecular Properties and Optogenetic Applications of Enzymerhodopsins
Molecular Properties and Optogenetic Applications of Enzymerhodopsins
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酶视紫红质的分子特性和光遗传学应用
DOI：
10.1007/978-981-15-8763-4_9
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Kandori Hideki
中科院分区：
文献类型：
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作者：
Tsunoda Satoshi P.;Sugiura Masahiro;Kandori Hideki
环核苷酸cAMP和cGMP是普遍存在的第二信使，其调节多种生物学功能，包括基因表达、分化、增殖和细胞存活。在感觉神经元中，环核苷酸负责信号调制、放大和编码。对于环核苷酸动力学的空间和时间操纵，光遗传学比药理学方法具有很大的优势。酶视紫红质是一个独特的微生物视紫红质家族。这些分子由膜包埋的视紫红质结构域和细胞质水溶性催化结构域组成，所述视紫红质结构域结合全反式视黄醇以形成发色团。迄今为止，已经从低等真核生物如真菌、藻类和鞭毛虫中鉴定出三种分子。其中，组氨酸激酶视紫红质（HKR）是一种光抑制鸟苷酸环化酶。视紫红质GC（Rh-GC）作为光活化鸟苷酸环化酶发挥作用，而视紫红质PDE（Rh-PDE）作为降解cAMP和cGMP的光活化磷酸二酯酶发挥作用。这些酶视紫红质在光遗传学应用中具有巨大的潜力，用于操纵活细胞的细胞内环核苷酸动力学。在这里我们介绍这些分子的分子功能和适用性。
The cyclic nucleotides cAMP and cGMP are ubiquitous secondary messengers that regulate multiple biological functions including gene expression, differentiation, proliferation, and cell survival. In sensory neurons, cyclic nucleotides are responsible for signal modulation, amplification, and encoding. For spatial and temporal manipulation of cyclic nucleotide dynamics, optogenetics have a great advantage over pharmacological approaches. Enzymerhodopsins are a unique family of microbial rhodopsins. These molecules are made up of a membrane-embedded rhodopsin domain, which binds an alltrans-retinal to form a chromophore, and a cytoplasmic water-soluble catalytic domain. To date, three kinds of molecules have been identified from lower eukaryotes such as fungi, algae, and flagellates. Among these, histidine kinase rhodopsin (HKR) is a light-inhibited guanylyl cyclase. Rhodopsin GC (Rh-GC) functions as a light-activated guanylyl cyclase, while rhodopsin PDE (Rh-PDE) functions as a light-activated phosphodiesterase that degrades cAMP and cGMP. These enzymerhodopsins have great potential in optogenetic applications for manipulating the intracellular cyclic nucleotide dynamics of living cells. Here we introduce the molecular function and applicability of these molecules.