Nucleoside transporter and nucleotide vesicular transporter: Two examples of mnemonic regulation

Abstract

According to their relevant roles in the regulation and availability of extracellular levels of purinergic signals, the nucleoside transporter and the nucleotide vesicular transporter are subject to acute regulation. The plasma membrane nucleoside transporter has been shown to exhibit several regulatory mechanisms, such as regulation by long-term signals, phosphorylation/dephosphorylation processes, and allosteric modulation. The present work reviews studies concerning allosteric modulation of nucleoside and nucleotide vesicular transporters, as the first reported examples of mnemonic behavior in transporter proteins, presenting kinetic and allosteric cooperativity. This fact implies that the protein can exhibit different conformations, each one with specific kinetic parameters. Transport substrates are able to induce slow conformational changes between the different forms of the transporter. This kinetic mechanism can provide several physiological advantages, since it allows strict control of transport capacity by changes in substrate concentrations. This allosteric modulation has been confirmed in several experimental models, the nucleoside transporter in chromaffin and endothelial cells from adrenal medulla and the nucleotide vesicular transporter in the chromaffin cell granules and rat brain synaptic vesicles. Taking into account these considerations, the mnemonic regulation described here could be a widespread mechanism among transporter proteins. Drug Dev. Res. 52:11-21, 2001.

NTPDase1 and NTPDase2 Immunolocalization in Mouse Cochlea: Implications for Regulation of P2 Receptor Signaling

“…These enzymes are likely the key elements for termination of P2 receptor signaling in the cochlea. NTPDases may prevent receptor desensitization by the hydrolysis of extracellular nucleotides (Enjyoji et al 1999), and NTPDase1, jointly with ecto-5′-nucleotidase, facilitates the salvage of adenosine via nucleoside transporters (Plesner 1995; Sen et al 2001). The aim of this study was to provide immunocytochemical localization of NTPDase1 and NTPDase2 expression in mouse cochlear tissues, extending the evidence for tissue-specific modulation of P2 receptor signaling.…”