A method for constructing light-sensitive membrane proteins that allow the manipulation of neuronal activity in vitro is reported online this week in Nature Methods.
Using light-sensitive proteins and corresponding light stimuli, the activity of neurons can be controlled. Continuous efforts are aimed to engineer new light-sensitive proteins with improved capabilities for neuron control for both basic research and future gene-therapy applications.
Ernst Bamberg and colleagues developed a protein-engineering strategy that consists of fusing the genes of two light-sensitive microbial proteins to create a hybrid protein. This strategy ensures co-localization and equal expression of the two proteins in the cell, which allows for both activation and inhibition of certain neurons with high precision and will aid in the study of the effects on brain function and behavior.
Bamberg and colleagues used the approach to also create engineered proteins capable of responding to a wider light spectrum. They made a light-sensitive protein capable of activating neurons in response to ‘white’ light, which might be of interest for ongoing gene-therapeutic visual restoration efforts. These new protein variants have yet to be tested in animal models in vivo.