Evidence for allosteric regulation of pH-sensitive System A (SNAT2) and System N (SNAT5) amino acid transporter activity involving a conserved histidine residue.

The Biochemical Journal
F E BairdP M Taylor

Abstract

System A and N amino acid transporters are key effectors of movement of amino acids across the plasma membrane of mammalian cells. These Na+-dependent transporters of the SLC38 gene family are highly sensitive to changes in pH within the physiological range, with transport markedly depressed at pH 7.0. We have investigated the possible role of histidine residues in the transporter proteins in determining this pH-sensitivity. The histidine-modifying agent DEPC (diethyl pyrocarbonate) markedly reduces the pH-sensitivity of SNAT2 and SNAT5 transporters (representative isoforms of System A and N respectively, overexpressed in Xenopus oocytes) in a concentration-dependent manner but does not completely inactivate transport activity. These effects of DEPC were reversed by hydroxylamine and partially blocked in the presence of excess amino acid substrate. DEPC treatment also blocked a reduction in apparent affinity for Na+ (K0.5Na+) of the SNAT2 transporter at low external pH. Mutation of the highly conserved C-terminal histidine residue to alanine in either SNAT2 (H504A) or SNAT5 (H471A) produced a transport phenotype exhibiting reduced, DEPC-resistant pH-sensitivity with no change in K0.5Na+ at low external pH. We suggest that the p...Continue Reading

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Citations

Nov 7, 2013·Pflügers Archiv : European journal of physiology·Stefan Bröer
Sep 27, 2013·Database : the Journal of Biological Databases and Curation·Kim Van RoeyToby J Gibson
Jul 25, 2008·Journal of the American Society of Nephrology : JASN·Kate EvansAlan Bevington
Mar 5, 2013·Annual Review of Biophysics·André SchönichenDiane L Barber
May 29, 2014·Journal of Neurovirology·Fabián J Vázquez-SantiagoVanessa Rivera-Amill
May 19, 2011·Journal of Pharmaceutical Sciences·Masanori TachikawaKen-ichi Hosoya
Jul 23, 2009·American Journal of Physiology. Endocrinology and Metabolism·Fiona E BairdPeter M Taylor
Nov 27, 2020·Frontiers in Cell and Developmental Biology·Geetha Venkateswaran, Shoukat Dedhar
Oct 13, 2020·The Journal of Physical Chemistry Letters·Amit Kumawat, Suman Chakrabarty
Jan 31, 2007·Biochemistry·Graciela Piwien PilipukMario D Galigniana

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