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

According to their relevant roles in the regulation and availability of ext racellular levels of purinergic signals, the nucleoside transporter and the nucleotide vesicular transporter are subject to acute regulation. The plas ma membrane nucleoside transporter has been shown to exhibit several regula tory mechanisms, such as regulation by long-term signals, phosphorylation/d ephosphorylation processes, and allosteric modulation. The present work rev iews 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, eac h one with specific kinetic parameters. Transport substrates are able to in duce slow conformational changes between the different forms of the transpo rter. This kinetic mechanism can provide several physiological advantages, since it allows strict control of transport capacity by changes in substrat e concentrations. This allosteric modulation has been confirmed in several experimental models, the nucleoside transporter in chromaffin and endotheli al cells from adrenal medulla and the nucleotide vesicular transporter in t he chromaffin cell granules and rat brain synaptic vesicles. Taking into ac count these considerations, the mnemonic regulation described here could be a widespread mechanism among transporter proteins. Drug Dev. Res. 52:11-21 , 2001. (C) 2001 Wiley-Liss, Inc.