Keeping it simple, transport mechanism and pH regulation in Na+/H+ exchangers
- 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.
Author: | Octavian CălinescuORCiDGND, Cristina Batista PaulinoORCiDGND, Werner KühlbrandtORCiDGND, Klaus FendlerORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-770004 |
DOI: | https://doi.org/10.1074/jbc.M113.542993 |
ISSN: | 0021-9258 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/24644283 |
Parent Title (English): | Journal of biological chemistry |
Publisher: | American Society for Biochemistry and Molecular Biology Publications |
Place of publication: | Bethesda, Md |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2021/01/04 |
Year of first Publication: | 2014 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2023/11/16 |
Tag: | Archaea; Cation Proton Antiporter; EcNhaA; Electrophysiology; Membrane Transport; MjNhaP1; Sodium Proton Exchange; Solid Supported Membrane; pH Regulation |
Volume: | 289 |
Issue: | 19 |
Page Number: | 9 |
First Page: | 13168 |
Last Page: | 13176 |
HeBIS-PPN: | 516511785 |
Institutes: | Biowissenschaften |
Biochemie, Chemie und Pharmazie / Biochemie und Chemie | |
Angeschlossene und kooperierende Institutionen / MPI für Biophysik | |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - CC BY - Namensnennung 4.0 International |