Topology of the Retinal Cone NCKX2 Na/Ca−K Exchanger
Abstract
The Na/Ca-K exchanger (NCKX) is a polytopic membrane protein that plays a critical role in Ca(2+) homeostasis in retinal rod and cone photoreceptors. The NCKX1 isoform is found in rods, while the NCKX2 isoform is found in cones, in retinal ganglion cells, and in various parts of the brain. The topology of the Na/Ca-K exchanger is thought to consist of two large hydrophilic loops and two sets of transmembrane spanning segments (TMs). The first large hydrophilic loop is located extracellularly at the N-terminus; the other is cytoplasmic and separates the two sets of TMs. The TMs consist of either five and five membrane spanning helices or five and six membrane spanning helices, depending upon the predictive algorithm used. Little specific information is yet available on the orientation of the various membrane spanning helices and the localization of the short loops connecting these helices. In this study, we have determined which of the connecting loops are exposed to the extracellular milieu using two different methods: accessibility of substituted cysteine residues and insertion of N-glycosylation sites. The two methods resulted in a consistent NCKX topology in which the two sets of TMs each contain five membrane spanning helices. Our new model places what was previously membrane spanning helix six in the cytoplasm, which places the C-terminus on the extracellular surface. Surprisingly, this NCKX topology model is different from the current NCX topology model with respect to the C-terminal three membrane helices.
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The experimentally determined topology for NCKX2 suggests that the polymorphic residue of NCKX5 sits in a transmembrane domain.
“This region contains a number of residues that are critical for exchange function (14 -16), and the experimentally determined topology for NCKX2 suggests that the polymorphic residue of NCKX5 sits in a transmembrane domain (17).”
From SLC24A5 encodes a trans-Golgi network protein with potassium-dependent sodium-calcium exchange activity that regulates human epidermal melanogenesis (2008) · cites this paper as [17]
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- Authors
- Kinjo, T. G., Szerencsei, R. T., Winkfein, R. J., Kang, K., & Schnetkamp, P. P. M.
- Affiliations
- University of Calgary (CA)
- Corresponding author
- Schnetkamp, Paul P. M.
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2003-02-04
- Volume
- 42
- Issue
- 8
- Pages
- 2485-2491
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- OpenAlex
- W2006317626
- Cited by
- 45
- References
- 7
- Citations by year
- 2025: 1 · 2024: 1 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 4 · 2012: 3
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- NCKX2, protein topology, cone photoreceptors, cysteine accessibility, polytopic membrane proteins
- MeSH terms
- Amino Acid Sequence, Animals, Cell Line, Cell Membrane, Cysteine, Extracellular Space, Glycosylation, Humans, Models, Molecular, Molecular Sequence Data, Moths, Rod Cell Outer Segment, Transfection, Mutagenesis, Site-Directed, Protein Structure, Secondary, Retinal Cone Photoreceptor Cells, Sodium-Calcium Exchanger, Amino Acid Substitution
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