Receptor tyrosine kinases (RTKs) are a family of cell-surface receptors that regulate critical cellular processes in normal health and disease. In a study published on June 9 in Nature Methods, Vladislav Verkhusha, Ph.D., and colleagues have developed an innovative approach for engineering light-sensitive RTKs whose activity can be specifically and reversibly controlled with light. This advance allows for the study of RTK downstream signaling pathways in various tissues and organs in living animals that, when dysregulated in the brain, have been implicated in sleep disorders, depression, and neurodegenerative diseases.

The researchers used a bacterial phytochrome as a light-sensing module that was molecularly connected to catalytic domains of RTKs. The eight resulting optogenetic RTK constructs were noninvasively turned on with far-red light and turned off with near-infrared light that deeply penetrates tissues. After expressing one of the RTKs in the brains of living mice and then stimulating it with far-red light through the skull, the researchers were able to induce neuronal activity and cell signaling in the neocortexes of the animals.

This approach for designing optically controlled RTKs can be used to engineer many other light-controllable receptors including cytokine receptors, hormone receptors, leptin receptors, and receptors of the immune system.

Dr. Verkhusha is professor of genetics and co-director of the Gruss Lipper Biophotonics Center at Einstein.

Albert Einstein College of Medicine has filed patent applications related to this research and is seeking licensing partners able to further develop and commercialize this technology. Interested parties can contact the Office of Biotechnology and Business Development at biotech@einsteinmed.edu