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Titolo:
Ligand-induced internalization of CD38 results in intracellular Ca2+ mobilization: role of NAD(+) transport across cell membranes
Autore:
Zocchi, E; Usai, C; Guida, L; Franco, L; Bruzzone, S; Passalacqua, M; De Flora, A;
Indirizzi:
Univ Genoa, Inst Biochem, I-16132 Genoa, Italy Univ Genoa Genoa Italy I-16132 Genoa, Inst Biochem, I-16132 Genoa, Italy Natl Res Council, Inst Cybernet & Biophys, I-16149 Genoa, Italy Natl Res Council Genoa Italy I-16149 net & Biophys, I-16149 Genoa, Italy
Titolo Testata:
FASEB JOURNAL
fascicolo: 2, volume: 13, anno: 1999,
pagine: 273 - 283
SICI:
0892-6638(199902)13:2<273:LIOCRI>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYCLIC-ADP-RIBOSE; SEA-URCHIN EGGS; ANTIGEN CD38; SURFACE; PROTEIN; NAD+; GLYCOHYDROLASE; IDENTIFICATION; GLYCOPROTEIN; ERYTHROCYTES;
Keywords:
pyridine nucleotides; cyclic ADP-ribose; intracellular calcium homeostasis; NAD(+) transporter;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: De Flora, A Univ Genoa, Inst Biochem, Viale Benedetto XV-1, I-16132 Genoa,Italy Univ Genoa Viale Benedetto XV-1 Genoa Italy I-16132 oa, Italy
Citazione:
E. Zocchi et al., "Ligand-induced internalization of CD38 results in intracellular Ca2+ mobilization: role of NAD(+) transport across cell membranes", FASEB J, 13(2), 1999, pp. 273-283

Abstract

CD38, a transmembrane glycoprotein widely expressed in vertebrate cells, is a bifunctional ectoenzyme catalyzing the synthesis and hydrolysis of cyclic ADP-ribose (cADPR). cADPR is a universal second messenger that releases calcium from intracellular stores. Since cADPR is generated by CD38 at the outer surface of many cells, where it acts intracellularly, increasing attention is paid to addressing this topological paradox. Recently, we demonstrated that CD38 is a catalytically active, unidirectional transmembrane transporter of cADPR, which then reaches its receptor-operated intracellular calcium stores. Moreover, CD38 was reported to undergo a selective and extensive internalization through non clathrin-coated endocytotic vesicles upon incubating CD38(+) cells with either NAD(+) or thiol compounds: these endocytotic vesicles can convert cytosolic NAD into cADPR despite an asymmetric unfavorable orientation that makes the active site of CD38 intravesicular. Here we demonstrate that the cADPR-generating activity of the endocytotic vesicles results in remarkable and sustained increases of intracellular free calcium concentration in different cells exposed to either NAD(+), or GSH, or N-acetylcysteine. This effect of CD38-internalizing Ligands on intracellular calcium levels was found to involve a two-step mechanism: 1) influx ofcytosolic NAD(+) into the endocytotic vesicles, mediated by a hitherto unrecognized dinucleotide transport system that is saturable, bidirectional, inhibitable by 8-N-3-NAD(+), and characterized by poor dinucleotide specificity, low affinity, and high efficiency; 2) intravesicular CD38-catalyzed conversion of NAD+ to cADPR, followed by out-pumping of the cyclic nucleotideinto the cytosol and subsequent release of calcium from thapsigargin-sensitive stores. This unknown intracellular trafficking of NAD(+) and cADPR based on two distinctive and specific transmembrane carriers for either nucleotide can affect the intracellular calcium homeostasis in CD38(+) cells.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/09/20 alle ore 05:43:08