Inglés-Prieto, Á. et al. Nat. Chem. Biol. doi:10.1038/nchembio.1933 (12 October 2015).

Optogenetic tools are being used increasingly for photocontrol of biological systems with high spatiotemporal precision. Inglés-Prieto et al. now expand the domain of optogenetics to high-throughput drug screening. Specifically, they study the mitogen-activated protein kinase/extracellular signal–regulated kinase (MAPK/ERK) pathway, which is stimulated by the activation of receptor tyrosine kinases (RTKs). In their screen, they use RTKs fused to light-oxygen-voltage–sensing domains ('opto-RTKs') that are activated by light-dependent dimerization; light thus stimulates the MAPK/ERK pathway activity and downstream reporter expression. Because activation and readout are both optical, fewer steps and no additional activation reagents are necessary, enabling screening with low variability. The authors demonstrate the power of their technique for several opto-RTKs, including 'orphan receptors' for which activating ligands are unknown.