Optogenetics techniques, which allow
scientists to map and control nerve cells using light stimulation, are
being used to study neural circuits in the brain with unprecedented
precision. This revolutionary technology relies on light-sensitive
proteins such as channelrhodopsins, and researchers at UC Santa Cruz
have now determined the molecular mechanism involved in the
light-induced activation of one of these proteins.
The new findings, published July 3 in two papers in the Journal of Biological Chemistry,
can help scientists create tailor-made proteins optimized for use in
optogenetics, said David Kliger, senior author of both papers and a
professor of chemistry and biochemistry at UC Santa Cruz.
"Little was known about the functional mechanism of these proteins
even though they are widely used in optogenetics," Kliger said.
The researchers used fast laser spectroscopy to study the function of
Channelrhodopsin-2, which is found in a type of marine algae and is
widely used in optogenetics experiments. Channelrhodopsins are ion
channels that control the flow of ions across cell membranes. There are
many kinds of ion channels that serve different purposes in different
types of cells. Nerve signals involve ion flow across the membranes of
nerve cells, and the breakthrough of optogenetics was the discovery that
inserting the genes for light-gated ion channels such as
channelrhodopsin into neurons would make them fire in response to light.
The first paper describes the mechanism of channelrhodopsin function
in terms of intermediate states the protein goes through in the process
of opening the ion channel. In the second paper, the researchers showed
that the mechanism revealed in the first paper can explain patterns of
ion currents observed in optogenetics experiments.
"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," Kliger said.
There are several types of modifications that could be useful for
optogenetics, such as making the proteins more efficient so that less
light is needed to trigger currents in neurons, he said. In some cases,
researchers might want to speed up the channel opening or slow it down,
or they might want to speed up or slow down the channel closing.
Depending on the tissues being studied, they might also want to shift
the spectrum of light needed to activate the protein.
"These basic biophysics experiments can help in optimizing how the proteins function in optogenetics experiments," Kliger said.
Story Source:
The above post is reprinted from
materials provided by
University of California - Santa Cruz. The original item was written by Tim Stephens.
Note: Materials may be edited for content and length.
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