Optogenetics Protein Mechanics Characterized

Researchers at the University of California, Santa Cruz, have identified the molecular mechanism involved in the light-induced activation of channelrhodopsins — a discovery that could help scientists create proteins optimized for optogenetics.

Optogenetics uses light stimulation to map and control nerve cells to enable study of the brain's neural circuitry. Offering unprecedented insight into the human brain, this field's technologies are reliant on light-sensitive proteins.

The researchers used time-resolved absorption spectroscopy in the 340- to 650-nm range to study the function of channelrhodopsin-2. Originally found in a type of marine algae and now widely used in optogenetics experiments, the protein controls the flow of ions across cell membranes, activating or deactivating different cellular functions when stimulated by light.

"Little was known about the functional mechanism of these proteins even though they are widely used in optogenetics," said professor David Kliger. "It is exciting because this opens up a methodology to start selecting mutant proteins with properties optimized for optogenetics, which is important for brain research and for studying neurological processes in general.”

There are several types of modifications that could be useful for optogenetics, Kliger said, such as making the proteins more efficient so less light is needed to trigger currents in neurons. In some cases, researchers might want to speed or slow the channel opening, or they might want to speed or slow the channel closing. Depending on the tissues being studied, they might also want to shift the spectrum of light required to activate the protein.

The research was published in The Journal of Biological Chemistry (doi: 10.1074/jbc.M114.631614 and 10.1074/jbc.M115.653071).

For more information, visit www.ucsc.edu.