Schematic overview of RTK signaling controlled by optogenetic tools. (A). RTKs dimerize upon binding of the ligand (L) to the extracellular domain (ECD), stimulating the kinase activity located in the intracellular domain (ICD) and subsequently RTK downstream signaling. (B). The fusion of an optogenetic switch (S) to full-length RTKs can induce light-dependent dimerization and signal independent of ligand binding. (C). An optogenetic switch fused to the intracellular domain of RTKs can induce light-dependent dimerization of ICD and RTK signaling. (D). An optogenetic switch anchored to the plasma membrane and fused to the intracellular domain of RTKs can induce light-dependent dimerization of ICD at the plasma membrane, activating downstream signaling. (E). DrBphP fused to the ICD of RTKs can induce light-dependent dimerization of the ICD, activating downstream signaling. (F). Clustering indirectly using CRY2 (CLICR). Though clustering of CRY2 fused to a specific SH2 domain, endogenous RTKs can be targeted and activated independently of ligand stimulation. Abbreviations: CRY2, cryptochrome 2; DrBphP, Deinococcus radiodurans bacterial phytochrome; ECD, extracellular domain; ICD, intracellular domain; L, ligand; SH2, Src homology region 2.