Xenorhodopsin for optogenetics
Optogenetics will get a new molecular "starter"
Phys Tech blog on Naked Science website
The work on the study of the photosensitive NsXeR protein from the xenorhodopsin class was published in the journal Science Advances by an international team of scientists from MIPT, the Institute of Structural Biology and the Yulikh Research Center.
Optogenetics is a modern technique that uses light to control nerve or muscle cells in a living organism. It is most widely used in studies of the nervous system. Its accuracy is so high that it allows you to control individual nerve cells, "turning on" or "turning off" certain ways of transmitting information. In addition, similar methods are used to partially restore lost vision and hearing or to control muscle contraction.
The main "tools" of optogenetics are photosensitive proteins that are artificially embedded in the right cells. After embedding, the protein works on the cell surface and under the influence of light transfers ions through the cell membrane. If you embed such a protein in a neuron, then a properly selected light pulse can trigger a nerve signal or, conversely, drown out all signals – depending on which protein is used. By triggering signals from individual neurons, it is possible to simulate the work of certain areas of the brain, changing the behavior of the body. If you embed such proteins into muscle cells, then you can strain or relax them with an external signal.
The authors of the paper published in Science Advances described a new tool for optogenetics – the NsXeR protein from the xenorhodopsin class. It is able to activate individual neurons, forcing them to send preset signals to the nervous system under the influence of light. In addition to applications in nervous system research, xenorhodopsins can occupy a niche of muscle cell management. To activate these cells, it is desirable to exclude the transport of calcium ions, since muscle cells are especially sensitive to changes in its concentration. If you use proteins that do not selectively transfer different positive ions (including calcium), undesirable side effects will appear.
The open protein allows you to bypass the problem with uncontrolled calcium transfer: it is distinguished by its selectivity and pumps only protons into the cell when working. This makes it favorably different from the direct competitor of channel rhodopsin, which is now widely used in research: he tolerates any positive ions when working. In addition, xenorhodopsin works as a reliable "pump", pumping protons regardless of their concentration on both sides of the membrane, and the channel rhodopsin only "opens" under the influence of light, allowing ions to go from a higher concentration to a lower one. In both cases, the flow of positive charges into the electrically excitable cell reduces the voltage between the outer and inner surface of the membrane. This depolarization of the membrane triggers a nerve or muscle impulse. The ability to launch such a pulse by pumping only protons will reduce potential side effects during research.
"At the moment, we have all the key information about the mechanism of the protein in our hands. This is the basis for further research on optimizing and adjusting protein parameters to the needs of optogenetics," says Vitaly Shevchenko, the first author of the work and an employee of the Laboratory for Advanced Research of membrane proteins at MIPT.
The work was supported by a grant from the Federal Target Program IR.
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26.09.2017