Molecular Cloning and Characterization of a Novel (Na+,K+)/H+ Exchanger Localized to the trans-Golgi Network
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The luminal pH of organelles along the secretory and endocytic pathways of mammalian cells is acidic and tightly regulated, with the [H+] varying up to 100-fold between compartments. Steady-state organellar pH is thought to reflect a balance between the rates of H+ pumping by the vacuolar-type H+-ATPase and H+ efflux through ill-defined pathways. Here, we describe the cloning of a novel gene (NHE7) in humans that is homologous to Na+/H+ exchangers, is ubiquitously expressed, and localizes predominantly to the trans-Golgi network. Significantly, NHE7 mediates the influx of Na+ or K+ in exchange for H+. The activity of NHE7 was also found to be relatively insensitive to inhibition by amiloride but could be antagonized by the analogue benzamil and the unrelated compound quinine. Thus, NHE7 displays unique functional and pharmacological properties and may play an important role in maintaining cation homeostasis of this important organelle.
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NHE7 is located in the TGN and post-Golgi vesicles and is differentially expressed in light and dark NHM.
“In addition, the Na ϩ /H ϩ exchanger NHE7 is located in the TGN and post-Golgi vesicles (35,36) and is differentially expressed in light and dark NHM (37) melanosomal pH could also be applied to the TGN.”
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 [35]
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- Authors
- Numata, M., & Orlowski, J.
- Affiliations
- McGill University (CA)
- Corresponding author
- Orlowski, John
- ORCID
- Orlowski, John
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-05
- Volume
- 276
- Issue
- 20
- Pages
- 17387-17394
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2033279834
- Cited by
- 244
- References
- 63
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 6 · 2022: 6 · 2021: 5 · 2020: 8 · 2019: 3 · 2018: 5 · 2017: 1 · 2016: 7 · 2015: 6 · 2014: 6 · 2013: 6 · 2012: 7
- FWCI
- 9.54
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship@McGill (McGill) (submittedVersion)
- eScholarship@McGill (McGill) (submittedVersion, cc-by)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- Na+/H+ exchanger, trans-Golgi network, cation homeostasis, vacuolar H+-ATPase, benzamil, quinine, gene cloning, secretory pathway
- MeSH terms
- Amino Acid Sequence, Animals, Carrier Proteins, Cloning, Molecular, Cricetinae, Humans, Hydrogen-Ion Concentration, Models, Molecular, Molecular Sequence Data, Potassium, Recombinant Proteins, Sodium, Transfection, Sequence Alignment, CHO Cells, Sequence Homology, Amino Acid, Protein Structure, Secondary, Antiporters, Sodium-Hydrogen Exchangers, Protein Isoforms, trans-Golgi Network, Membrane Transport Proteins
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