Dimeric and tetrameric forms of catalytically active transmembrane CD38 in transfected HeLa cells

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 me 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, (C) 1998 Federation of European Biochemical Societies.