A new optogenetic tool, a light-controllable protein, has been characterized by researchers at the Ruhr-Universität Bochum (RUB). They used an opsin – a protein found in the brain and eyes – from zebrafish and introduced it into the brains of mice. Unlike other optogenetic tools, this opsin is not turned on but turned off by light. Experiments have also shown that the tool could be adapted to study the changes in the brain that are responsible for the development of epilepsy.
Teams led by Professor Melanie Mark of the Behavioral Neurobiology Research Group and Professor Stefan Herlitze of the Department of General Zoology and Neurobiology describe the experiments and results in the journal Nature Communication, published online 23 July 2021.
Role assumed under various conditions
Opn7b opsin is a G protein coupled receptor found in zebrafish. Unlike many other light activated G protein coupled receptors, it can be activated without light stimulus and is therefore permanently active; researchers call it constitutively active. Normally, activation of G protein-coupled receptors leads to the opening of certain ion channels and thus to the influx of ions into the cell as well as other signaling processes in the cell. In the case of Opn7b, the light deactivates this permanently active signaling chain.
So far, little research has been done on G-protein-coupled receptors that are activated without stimulation, although it is suspected that they play a role in various neuropsychiatric conditions and night blindness. They also seem to be involved in the development of cancers of viral origin.
Receiver characterized more precisely
Dr Raziye Karapinar, Dr Ida Siveke and Dr Dennis Eickelbeck characterized in detail the function of Opn7b and, to their surprise, identified that the receptor is deactivated by light. In contrast, conventional optogenetic tools are turned on by light.
The researchers consider that Opn7b is well suited to better understand the function of G protein-coupled receptors that are constitutively active – and to gain new knowledge about their role in the development of diseases in which the receptors can be examined in a controlled time. way into specific cell types.
Bochum researchers Dr Jan Claudius Schwitalla and Johanna Pakusch modified some cells in the cerebral cortex of mice to produce Opn7b. If they turned off the receptor with light, it triggered epileptiform activity in animals, which could be specifically controlled by light and interrupted using other light-controlled proteins. The researchers hope that it will be possible to use this optogenetic tool to understand more precisely both the underlying mechanisms and the time scales in the development of epileptic seizures.
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Material provided by Ruhr-University of Bochum. Original written by Julia Weiler. Note: Content can be changed for style and length.