Figure 6.

Proposed mechanism for the UVR phototransduction cascade in HEMs. (A) UVR stimulates a G protein–coupled receptor in a retinal-dependent manner, and leads to activation of Gα_q/11 and PLCβ, which hydrolyzes PIP₂ into DAG and IP₃. PIP₂ hydrolysis regulates the activity of TRPA1 at the plasma membrane to mediate Ca²⁺ influx, whereas IP₃ activates IP₃R to mediate Ca²⁺ release from intracellular stores. The increase in intracellular Ca²⁺ leads to early melanin synthesis. (B) Predicted contribution of IP₃R- and TRPA1-mediated Ca²⁺ responses to UVR-induced Ca²⁺ signaling kinetics. IP₃R contributes to the rapid initial increase in Ca²⁺, whereas TRPA1 contributes to sustained Ca²⁺ influx.