CD38–Cyclic ADP-Ribose Signal System in Physiology, Biochemistry, and Pathophysiology

Calcium (Ca(2+)) is a ubiquitous and fundamental signaling component that is utilized by cells to regulate a diverse range of cellular functions, such as insulin secretion from pancreatic β-cells of the islets of Langerhans. Cyclic ADP-ribose (cADPR), synthesized from NAD(+) by ADP-ribosyl cyclase family proteins, such as the mammalian cluster of differentiation 38 (CD38), is important for intracellular Ca(2+) mobilization for cell functioning. cADPR induces Ca(2+) release from endoplasmic reticulum via the ryanodine receptor intracellular Ca(2+) channel complex, in which the FK506-binding protein 12.6 works as a cADPR-binding regulatory protein. Recently, involvements of the CD38-cADPR signal system in several human diseases and animal models have been reported. This review describes the biochemical and molecular biological basis of the CD38-cADPR signal system and the diseases caused by its abnormalities.