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Optical Switch Enables Control of Blind Neuroreceptor

An ERC Advanced Grant has been awarded to LMU chemist Dirk Trauner for a project based on optochemical genetics. By this innovative approach, artificial photoreceptors can be created by integrating neural receptor molecules with light-sensitive, synthetic switching factors.

The interactions of nerve cells give rise to receptor molecules at their surfaces that generate signals. Using acetylcholine, the conversion of an intrinsically blind receptor into a photoreceptor has been achieved by a group of chemists from the University of California in Berkeley and Ludwig-Maximilians-Universität (LMU) from Munich.

Professor Trauner and his colleagues used the nicotinic acetylcholine receptors that transmit nerve impulses by transforming the incoming chemical signals into an electrical response, generated along the nerve fiber. The neurotransmitter acetylcholine binds to the external surface of the receptor. This functions as a switch that leads to a tiny pore in the receptor. The positively charged sodium ions can flow into the cell through this receptor. The resulting depolarization creates the professed action potential.

The optochemical genetics is based on genetic manipulation technology, wherein a receptor protein is modified in order to bind to a synthetic, light-sensitive switching ligand, based on azobenzenes. A photosensitive double bond exists between nitrogen atoms. Upon illumination with monochromatic light of varying wavelengths, it undergoes alterations like bent and extended conformations. Trauner and his colleagues applied several targeted modifications into the gene that indicates the receptor’s amino acid sequence to ensure that the fixing of artificial switch and to verify the modifications needed to open and close the ion channel. Electrophysiological techniques validate the ability of cultured cells expressing the mutated gene. The cells were incubated with azobenzene compound. Radiation with green light closed the ion channel of the modified receptor, which upon illumination with violet light gets activated.

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