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Cytoskeleton, Intracellular Transport, Vesicle Traffic and Synaptic Function

Nucleotides are released as extracellular mediators in the brain and in other tissues. The actions of nucleotides on various P2 purinergic/pyrimidinergic receptors are terminated by ectonucleotidases by sequential extracellular metabolism to the respective nucleosides. Nucleoside triphosphate diphosphohydrolase-1 (NTPDase1/CD39) is the dominant ectonucleotidase of the vascular and placental trophoblastic tissues. Following palmitoylation at the N-terminal domain, NTPDase1/CD39 is directed to plasma membrane microdomains termed caveolae. Immunostaining and electron microscopy indicate that P2Y1 and P2Y2 G-proteincoupled receptors are localized within distinct areas of human placental tissue and are likewise targeted to membrane microdomains characteristic of caveolae. NTPDase1/CD39 can regulate nucleotide-mediated signaling events and thereby modulate functional expression of these receptors. The differential localization of P2Y1 and P2Y2 receptors in human placenta may indicate different roles in the regulation of extracellular nucleotide concentrations.