CoChat
Sign Up
Cited by 46Ion channel regulation and functionIon Transport and Channel RegulationCardiac electrophysiology and arrhythmias

Analysis of Ion Interactions with the K+ -dependent Na+/Ca+ Exchangers NCKX2, NCKX3, and NCKX4

Open access
Visser, Frank, Valsecchi, Valeria, Annunziato, Lucio, Lytton, Jonathan·2007·Journal of Biological Chemistry
DOI 10.1074/jbc.m610582200
Open this paper in CoChat — free accountOpen PDF

Abstract

K(+)-dependent Na(+)/Ca(2+) exchangers (NCKX) catalyze cytosolic Ca(2+) extrusion and are particularly important for neuronal Ca(2+) signaling. Of the five mammalian isoforms, the detailed functional characteristics have only been reported for NCKX1 and -2. In the current study, the functional characteristics of recombinant NCKX3 and -4 expressed in HEK293 cells were determined and compared with those of NCKX2. Although the apparent affinities of the three isoforms for Ca(2+) and Na(+) were similar, NCKX3 and -4 displayed approximately 40-fold higher affinities for K(+) ions than NCKX2. Functional analysis of various NCKX2 mutants revealed that mutation of Thr-551 to Ala, the corresponding residue in NCKX4, resulted in an apparent K(+) affinity shift to one similar to that of NCKX4 without a parallel shift in apparent Ca(2+) affinity. In the converse situation, when Gln-476 of NCKX4 was converted to Lys, the corresponding residue in NCKX2, both the K(+) and Ca(2+) affinities were reduced. These results indicate that the apparently low K(+) affinity of NCKX2 requires a Thr residue at position 551 that may reduce the conformational flexibility and/or K(+) liganding strength of side-chain moieties on critical neighboring residues. This interaction appears to be specific to the structural context of the NCKX2 K(+) binding pocket, because it was not possible to recreate the K(+)-specific low affinity phenotype with reciprocal mutations in NCKX4. The results of this study provide important information about the structure and function of NCKX proteins and will be critical to understanding their roles in neuronal Ca(2+) signaling.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1074/jbc.m610582200

Cites

40 of 40 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. Komuro, I., Wenninger, K. E., Philipson, K. D., and Izumo, S. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 4769 -4773
  2. Ausubel, F. M., Brent, R., Kingston, R. E., Moore, D. D., Seidman, J. G., Smith, J. A., and Struhl, K. (eds) (2006) Current Protocols in Molecular Biology, John Wiley & Sons, New York, NY

Cited by

Sorted by citations

Related

Authors
Visser, F., Valsecchi, V., Annunziato, L., & Lytton, J.
Affiliations
  • University of Calgary (CA)
  • University of Naples Federico II (IT)
Corresponding author
Lytton, Jonathan
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2007-02
Volume
282
Issue
7
Pages
4453-4462
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.m610582200
OpenAlex
W1990666241
Cited by
46
References
40
Citations by year
2022: 2 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 4 · 2016: 5 · 2015: 3 · 2014: 2 · 2013: 4 · 2012: 3
FWCI
1.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • INFM-OAR (INFN Catania) (submittedVersion, cc-by)
Funders
  • Fondation pour la Recherche Médicale
  • Canadian Institutes of Health Research
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
Keywords
NCKX2, neuronal calcium signaling, site-directed mutagenesis
MeSH terms
Binding Sites, Calcium, Cell Line, Humans, Potassium, Protein Conformation, Structure-Activity Relationship, Mutagenesis, Site-Directed, Antiporters, Sodium-Calcium Exchanger, Calcium Signaling, Mutation, Missense

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review