Nucleoside triphosphate diphosphohydrolases in extracellular nucleotide regulation: activity, structural insights, and pathophysiological implications

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Résumé

In this chapter, we review the ecto-nucleoside triphosphate diphosphohydrolase (NTPDase) family, a group of ectonucleotidases that regulate nucleotide signaling by hydrolyzing extracellular nucleotides such as ATP, ADP, UTP, and UDP. Among the eight NTPDase members, NTPDase1, -2, -3, and -8 are cell membrane-bound, while NTPDase4, -5, -6, and -7 are mostly localized to intracellular compartments. By hydrolyzing nucleotides in the extracellular milieu, NTPDases influence diverse pathophysiological processes. We focus on human cell membrane-bound NTPDases, detailing their substrate specificity, structural features, posttranslational modifications, tissue distribution, and implications in health and disease, including thromboregulation, cardiovascular diseases, neuroinflammation, cancer, and inflammatory bowel disease.

Mots-clés

Ectonucleotidases; extracellular nucleotides; ATP hydrolysis; P2 receptors; nucleotide signaling; pathophysiology; inflammatory disorders; vascular homeostasis; intestinal inflammation; nucleoside triphosphate diphosphohydrolases (NTPDases)