LANCL2 is necessary for Abscisic acid binding and signaling in human granulocytes and in rat insulinoma cells

Abscisic acid (ABA) is a plant hormone regulating fundamental physiological functions in plants, such as response to abiotic stress. Recently, ABA was shown to be produced and released by human granulocytes, by insulin-producing rat insulinoma cells and by human and murine pancreatic beta cells. ABA autocrinally stimulates the functional activities specific for each cell type through a receptor-operated signal transduction pathway, sequentially involving a pertussis toxin (PTX)-sensitive receptor/G-protein complex, cyclic AMP, CD38-produced cyclic ADP-ribose and intracellular calcium. Here, the ABA receptor on human granulocytes and on rat insulinoma cells is identified as the lanthionine synthetase C-like protein LANCL2. Co-expression of LANCL2 and CD38 in the human HeLa cell line reproduces the ABA-signaling pathway. Results obtained with granulocytes and CD38+/LANCL2+ HeLa transfected with a chimeric G protein (Galphaq/i) suggest that the PTX-sensitive G protein coupled to LANCL2 is a Gi. Identification of the mammalian ABA receptor will enable the screening of synthetic ABA antagonists as prospective new anti-inflammatory and anti-diabetic agents.