Zocchi E, Franco L, Guida L, Piccini D, Tacchetti C, De Flora A
Institute of Biochemistry, University of Genoa, Italy.
FEBS Lett. 1996 Nov 4;396(2-3):327-32. doi: 10.1016/0014-5793(96)01125-8.
CD38 is a transmembrane glycoprotein involved as an orphan receptor in many physiological processes of lymphocytes. It is also a bifunctional enzyme that catalyzes at its ectocellular domain the synthesis from NAD+ (cyclase) and the hydrolysis (hydrolase) of the calcium-mobilizing metabolite cyclic ADP-ribose (cADPR). A still unexplained paradox concerns the relationship between ectocellular localization of CD38 and 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 internalization in non-clathrin-coated vesicles. Since the internalized CD38 was demonstrated to be enzymatically active, this NAD+-dependent process is a hitherto unrecognized means for shifting cADPR metabolism from the cell surface to the intracellular environment.
CD38是一种跨膜糖蛋白，作为孤儿受体参与淋巴细胞的许多生理过程。它也是一种双功能酶，在其胞外结构域催化由NAD⁺合成（环化酶）以及水解（水解酶）可动员钙的代谢物环磷酸腺苷核糖（cADPR）。一个尚未得到解释的矛盾涉及CD38的胞外定位与其中间产物cADPR的细胞内钙释放活性之间的关系。用细胞外NAD⁺孵育CD38⁺人Namalwa B细胞会引起CD38广泛的膜下调及其在非网格蛋白包被小泡中的内化。由于内化的CD38被证明具有酶活性，这种依赖NAD⁺的过程是一种迄今未被认识的将cADPR代谢从细胞表面转移到细胞内环境的方式。
