NAD+-dependent internalization of the transmembrane glycoprotein CD38 in human Namalwa B cells.
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.
Institute of Biochemistry, University of Genoa, Italy.
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Zocchi
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Franco
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Guida
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Piccini
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Tacchetti
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De Flora
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives / Q000378:metabolism; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism*; D001402:B-Lymphocytes / Q000201:enzymology* / Q000648:ultrastructure; D002462:Cell Membrane / Q000201:enzymology*; D036563:Cyclic ADP-Ribose; D015536:Down-Regulation; D004705:Endocytosis; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D008562:Membrane Glycoproteins; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D009243:NAD / Q000494:pharmacology*; D015388:Organelles / Q000201:enzymology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D009243:NAD; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D005978:Glutathione