Fresh from a Nobel Prize win in Chemistry for his work with green fluorescent protein (GFP), Roger Tsien shows no sign of slowing down.
One of the latest tools from his laboratory, dubbed ChIEF, is described in a recent issue of the Biophysical Journal. In this case, the goal is an engineered protein to facilitate photostimulation of neurons. Light-gated channelrhodopsins can be induced by bursts of blue light to propagate action potentials; this exogenous control of neuronal excitation has applications from mapping neuronal circuits to modulating neural activity.
Chlamydomonas channelrhodopsin (ChR)2, which is a nonselective cation channel, is more widely used than ChR1, which shows bias for protons. However, ChR1 outperforms ChR2 in being less rapidly inactivated by ongoing light exposure.
Using elements of ChR1 and ChR2 and site-directed mutagenesis, Lin et al. design a best-of-both-worlds chimera, ChIEF. This new variant shows nearly 3 times less inactivation than ChR2, making it more responsive to light pulses of 25 Hz or higher, the type of stimulus generally required to trigger action potential chains.
Notably, the improved temporal precision does not come with the downsides of ChR1, as ChIEF conducts cations other than protons and so does not require acidic buffer conditions. Like the many flavors of fluorescent proteins Tsien’s lab has pioneered, this engineered light-gated channel promises to become a tool that is widely and creatively applied.
Lin et al. 2009. Characterization of engineered channelrhodopsin variants with improved properties and kinetics. Biophys J 96:1803-1814.
