Bruzzone S, Guida L, Franco L, Zocchi E, Corte G, De Flora A
Institute of Biochemistry, University of Genoa, Italy.
FEBS Lett. 1998 Aug 21;433(3):275-8. doi: 10.1016/s0014-5793(98)00929-6.
CD38, a type II transmembrane glycoprotein, behaves as a catalytically active transporter responsible for ectocellular generation of cyclic ADP-ribose (cADPR) from NAD+ and for subsequent influx of cADPR across membranes [Franco, L., Guida, L., Bruzzone, S., Zocchi, E., Usai, C. and De Flora, A. (1998) FASEB J. in press]. cADPR regulates intracellular calcium homeostasis by releasing calcium from responsive stores. The cADPR-transporting function of CD38 requires channel-generating oligomeric forms of the protein rather than the 46 kDa monomers that have been described so far in CD38+ cells. Here we demonstrate that CD38, both in reconstituted proteoliposomes and in CD38-transfected HeLa cells, is a mixture of catalytically active monomers, homodimers and homotetramers. A soluble recombinant form of CD38 corresponding to its ectocellular region proved to be monomeric. Thus, association of native CD38 with either artificial or natural membranes seems to result in a reversible juxtaposition of monomers suitable to cADPR-transporting activity.
CD38是一种II型跨膜糖蛋白，作为一种具有催化活性的转运蛋白，负责从NAD+胞外生成环磷酸腺苷核糖（cADPR），并随后使cADPR跨膜内流[佛朗哥，L.，吉达，L.，布鲁佐内，S.，佐基，E.，乌赛，C.和德弗洛拉，A.（1998年）《美国实验生物学会联合会杂志》即将发表]。cADPR通过从反应性储存库中释放钙来调节细胞内钙稳态。CD38的cADPR转运功能需要该蛋白形成通道的寡聚体形式，而不是迄今在CD38+细胞中所描述的46 kDa单体。在此，我们证明，无论是在重组蛋白脂质体中还是在CD38转染的HeLa细胞中，CD38都是具有催化活性的单体、同型二聚体和同型四聚体的混合物。一种对应于其胞外区域的可溶性重组形式的CD38被证明是单体。因此，天然CD38与人工膜或天然膜的结合似乎导致单体可逆并列，适合cADPR转运活性。
