Lysophosphatidic acid (LPA) is a bioactive lipid molecule with a phosphate, a glycerol, and a fatty acid in its structure. The cellular effects of LPA include proliferation, migration, cytokine secretion, and morphological change. These pleiotropic actions allow LPA to participate in a wide variety of biological processes, such as brain development, oncogenesis, wound healing and cancer progression¹. To date, at least 6 subtypes of LPA receptors have been identified. The LPA1-3 receptors are members of the endothelial cell differentiation gene (Edg) family². All six receptors are type I, rhodopsin-like G-protein coupled receptors (GPCRs) that differ in their tissue distribution and downstream signaling pathways³.

GPCRs share a similar topology, with seven transmembrane helices (TMHs) connected by three extracellular loops (ECLs), and three intracellular loops (ICLs); the N-terminus is on the extracellular side of the membrane, and the C-terminus is on the cytoplasmic side⁴.

Expression of LPA3 receptor has been observed in human heart, testis, prostate, pancreas, lung, ovary, and brain⁵ and is most abundant in mouse testis, kidney, lung, small intestine, heart, stomach, spleen, brain, and thymus⁶.

LPA3 receptor null mice are viable and grossly normal, but female nulls show a striking phenotype in the reproductive system⁷. However, despite the fact that LPA3 is expressed in the frontal cortex, hippocampus, and amygdala, no phenotypes related to LPA3 loss in the nervous system have been reported to date⁵.