LPA₃, a unique G protein-coupled receptor for lysophosphatidic acid

Lysophosphatidic acid (LPA; 1- or 2-acyl-sn-glycerol-3-phosphate) is a phospholipid that is involved in numerous normal physiological and pathological processes such as brain development, blood vessel formation, embryo implantation, hair growth, neuropathic pain, lung fibrosis and colon cancer. Most of these functions are mediated by G protein-coupled receptors (GPCRs) specific to LPA. So far, six GPCRs for LPA have been identified: LPA ₁/Edg2, LPA₂/Edg4, LPA₃/Edg7, LPA ₄/GPR23/P2Y9, LPA₅/GPR92 and LPA₆/P2Y5. An intracellular target of LPA has also been proposed. Among the LPA receptors, LPA₃ is unique in that it is activated significantly by a specific form of LPA (2-acyl LPA with unsaturated fatty acids) and is expressed in a limited number of tissues such as the reproductive organs. Recent studies have shown that LPA₃-mediated LPA signaling is essential for proper embryo implantation and have revealed an unexpected genetic linkage between LPA and prostaglandin signaling. Here we review recent advances in the study of LPA ₃, especially studies using LPA₃-deficient mice. In addition, we focus on the agonists and antagonists that are specific to each LPA receptor as important tools for the functional study of LPA signaling.