Strategy for optogenetic control of ligand secretion. (A) Strategy for optogenetic triggering of ligand secretion. The target ligand is fused to the luminal side of a transmembrane protein (VSVG-ts045) and YFP and 2xUVR8 repeats on the cytoplasmic side. Before photoactivation (no PA), the construct forms clusters in the ER, with minimal trafficking to the Golgi. After photoactivation by UVB (PA), some fusion proteins get released and traffic to the Golgi whereby the target ligand is cleaved off by furin, leading to secretion of the desirable moiety in the extracellular medium. (B) Representation of cells in tissue before and after photoactivation. Target ligand gradient is shown in red. w/o, without.