TY  - JOUR
A1  - Călinescu, Octavian
A1  - Batista Paulino, Cristina
A1  - Kühlbrandt, Werner
A1  - Fendler, Klaus
T1  - Keeping it simple, transport mechanism and pH regulation in Na+/H+ exchangers
T2  - Journal of biological chemistry
N2  - Na(+)/H(+) exchangers are essential for regulation of intracellular proton and sodium concentrations in all living organisms. We examined and experimentally verified a kinetic model for Na(+)/H(+) exchangers, where a single binding site is alternatively occupied by Na(+) or one or two H(+) ions. The proposed transport mechanism inherently down-regulates Na(+)/H(+) exchangers at extreme pH, preventing excessive cytoplasmic acidification or alkalinization. As an experimental test system we present the first electrophysiological investigation of an electroneutral Na(+)/H(+) exchanger, NhaP1 from Methanocaldococcus jannaschii (MjNhaP1), a close homologue of the medically important eukaryotic NHE Na(+)/H(+) exchangers. The kinetic model describes the experimentally observed substrate dependences of MjNhaP1, and the transport mechanism explains alkaline down-regulation of MjNhaP1. Because this model also accounts for acidic down-regulation of the electrogenic NhaA Na(+)/H(+) exchanger from Escherichia coli (EcNhaA, shown in a previous publication) we conclude that it applies generally to all Na(+)/H(+) exchangers, electrogenic as well as electroneutral, and elegantly explains their pH regulation. Furthermore, the electrophysiological analysis allows insight into the electrostatic structure of the translocation complex in electroneutral and electrogenic Na(+)/H(+) exchangers.
KW  - Archaea
KW  - Electrophysiology
KW  - Membrane Transport
KW  - pH Regulation
KW  - Sodium Proton Exchange
KW  - EcNhaA
KW  - MjNhaP1
KW  - Cation Proton Antiporter
KW  - Solid Supported Membrane
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/77000
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-770004
SN  - 0021-9258
VL  - 289
IS  - 19
SP  - 13168
EP  - 13176
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -