Opsins and their testing in heterological expression systems

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Abstract

The study of photosensitive proteins as optogenetic tools for the therapeutic restoration of visual functions in heterologous expression systems is a necessary step prior to their optogenetic prosthetization in the retina. The review considers the features of opsins and factors affecting their activity in model cell systems. Particular attention is paid to G-protein-coupled opsins as promising tools for recreating the signaling cascade mechanisms of in retinal ON-bipolar cells. Based on the analysis of light-controlled responses of natural and chemical light-sensitive proteins in tests, the selection of the best, promising in gene therapy is made.

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Y. A. Chiligina

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

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Email: julchil@mail.ru
Russian Federation, St. Petersburg

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2. Fig. 1. Scheme of the phototransduction cascade in the rod. (a) receptor activation in the light. As a result of photon absorption, receptor activation and signal transmission from the activated receptor (rhodopsin) to transducin occur; as a result of a cascade of reactions, non-selective cationic cGMP-dependent channels are closed. (b) receptor deactivation. Rhodopsin returns to the dark state as a result of sequential interactions: recoverin–rhodopsin kinase, rhodopsin kinase–activated receptor, arrestin–phosphorylated metarhodopsin, receptor blocking. (c) phosphodiesterase shutdown. RGS9-1 protein binds to the Gt*–PDE-6 complex, resulting in dissociation of the complex. R — rhodopsin, R* — activated rhodopsin, Gt — transducin, Gt* — activated transducin, GDP — guanosine diphosphate, GTP — guanosine triphosphate, PDE-6 — phosphodiesterase-6, cGMP — cyclic guanosine monophosphate, GMP — guanosine monophosphate, GC — guanylate cyclase, REC — recoverin, RK — rhodopsin kinase, Ap — arrestin, R*-P — phosphorylated metarhodopsin.

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3. Fig. 2. Scheme of TRPM1 channel activation in ON-bipolar cells. Designations: Glu — glutamate, mGluR6 — metabotropic receptor mGluR6 of ON-bipolar cells, TRPM1 — channel of transient receptor potential of subfamily M, GDP — guanosine diphosphate, GTP — guanosine triphosphate, NT — N-terminus, CT — C-terminus.

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