(A) Representation of the wild-type TrkA receptor. TrkA is a Type I transmembrane protein anchored at the plasma membrane by a single-helix transmembrane domain (TM). Nerve growth factor (NGF) associates with the extracellular domain (ECD) to promote receptor dimerization and phosphorylation of key tyrosines within the intracellular domain (ICD). Y670, Y674, and Y675 are critical for kinase activity, while Y490 and Y785 are involved in the initiation of the Raf/MEK/ERK and PLCγ-PKC signaling pathways, respectively. (B) Schematic representation of the optogenetic TrkA receptor. The ECD and TM are replaced by a lipidation motif to abolish ligand sensitivity, while retaining normal orientation and localization at the plasma membrane. Light sensitivity is introduced through fusion with the photosensitive protein, AuLOV. Illumination with blue light should promote dimerization of receptor ICDs and activation of downstream signaling pathways. Green fluorescent protein (GFP) serves as a probe for system expression.