NAD(-DEPENDENT INTERNALIZATION OF THE TRANSMEMBRANE GLYCOPROTEIN CD38IN HUMAN NAMALWA B-CELLS())

CD38 is a transmembrane glycoprotein involved as an orphan receptor in many physiological processes of lymphocytes. It is also a bifunctiona l enzyme that catalyzes at its ectocellular domain the synthesis from NAD(+) (cyclase) and the hydrolysis (hydrolase) of the calcium-mobiliz ing metabolite cyclic ADP-ribose (cADPR), A still unexplained paradox concerns the relationship between ectocellular localization of CD38 an d intracellular calcium-releasing activity of its intermediate product cADPR, Incubation of CD38(+) human Namalwa B cells with external NAD( +) elicited extensive membrane down-regulation of CD38 and its interna lization in non-clathrin-coated vesicles, Since the internalized CD38 was demonstrated to be enzymatically active, this NAD(+)-dependent pro cess is a hitherto unrecognized means for shifting cADPR metabolism fr om the cell surface to the intracellular environment.