Author links open overlay panel, Abstract

Animal opsin is a G-protein coupled receptor (GPCR) and binds retinal as a chromophore to form a photopigment. The Opsin 5 (Opn5) group within the animal opsin family comprises a diverse array of related proteins, such as Opn5m, a protein conserved across all vertebrate lineages including mammals, and other members like Opn5L1 and Opn5L2 found in non-mammalian vertebrate genomes, and Opn6 found in non-therian vertebrate genomes, along with Opn5 homologs present in invertebrates. Although these proteins collectively constitute a single clade within the molecular phylogenetic tree of animal opsins, they exhibit markedly distinct molecular characteristics in areas such as retinal binding properties, photoreaction, and G-protein coupling specificity. Based on their molecular features, they are believed to play a significant role in physiological functions. However, our understanding of their precise physiological functions and molecular characteristics is still developing and only partially realized. Furthermore, their unique molecular characteristics of Opn5 related proteins suggest a high potential for their use as optogenetic tools through more specialized manipulations. This review intends to encapsulate our current understanding of Opn5, discuss potential manipulations of its molecular attributes, and delve into its prospective utility in the burgeoning field of animal opsin optogenetics.

Section snippetsPhylogeny of animal opsins

Animal opsins are membrane proteins that belong to the superfamily of G-protein coupled receptors (GPCRs). Their activity is regulated by the binding of retinal and by light reception, and some have lost their G-protein activation ability and function as retinal photoisomerases.[3] The most extensively studied animal opsin is the visual pigment of vertebrates, particularly the rod visual pigment rhodopsin.[4] Since the research on rhodopsin by Boll and Kühne, rhodopsin has been actively studied

Possible modification of molecular properties and potential optogenetic use of Opn5 related proteins

Similar to the most frequently used channelrhodopsin-2 and microbial rhodopsins that function as light-driven ion transporters, animal opsins can be used as optogenetic tools to endow cells with light sensitivity and control their functions.65, 66 The use of animal opsins in optogenetics began with the use of well-understood vertebrate rhodopsins and their intracellular loop chimeras. 66, 67, 68 Recently, a wide variety of animal opsins including non-visual opsins and their mutants and chimeras

Manipulation of the molecular property of animal opsins

In animal opsins, which are class A GPCRs, coupling specificity for heterotrimeric G proteins can be manipulated by substituting the intracellular loops, particularly the third intracellular loop.72, 73 There are also reports that the proximal region of the C-terminal is important for the coupling specificity.74, 75 In addition to activation of various G proteins by replacing the intracellular loops of vertebrate rhodopsins 66, 76, 77, there have been reports on loop replacements in cone

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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