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 acro ss membranes [Franco, L., Guida, L., Bruzzone, S,, Zocchi, E,, Usai, C , and De Flora, A. (1998) FASEB J, in press]. cADPR regulates intracel lular calcium homeostasis by releasing calcium from responsive stores. The cADPR-transporting function of CD38 requires channel-generating o ligomeric forms of the protein rather than the 46 kDa monomers that ha ve been described so far in CD38(+) cells. Here me demonstrate that CD 38, 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 nati ve 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.