FIGURE 8.

A proposed model to depict the mechanism underlying the LPA₂-mediated gradient sensing and migration of fibroblasts in response to an extracellular LPA cue. A, a schematic representation of asymmetric Ca²⁺ puff activation in cells exposed to an LPA gradient. B, LPA-induced and LPA₂-mediated gradient sensing of fibroblasts is initiated through the asymmetric formation of LPA₂ complexes, which activate downstream asymmetric PLC-β3-inositol 1,4,5-trisphosphate/Ca²⁺ signaling to trigger Ca²⁺ puffs to guide the gradient sensing and migration of fibroblasts.