Levitz, J. et al. Nat. Neurosci. 16, 507–516 (2013).

Metabotropic glutamate receptors (mGluRs) play important roles in synaptic transmission between neurons. To develop tools for manipulating the function of specific mGLuRs in cells and tissues, Levitz et al. used an optochemical approach combining synthetic photoswitchable tethered ligands (PTLs) and engineered versions of the receptor. Using this strategy, they generated light-activated and light-inhibited versions of mGluR2 (LimGluRs). LimGluR2, when covalently bound by the PTL, becomes activated by a 380-nm light pulse and deactivated by a 500-nm pulse. In contrast, LimGluR2-block is inactivated when illuminated at 380 nm by the action of its PTL, which blocks binding of the endogenous ligand glutamate, and this inactivation is reversed at 500 nm. The tools trigger the same downstream signaling pathways as those of the endogenous mGluRs, and a single photoswitch is enough to keep them turned on or off as long as desired.