Skip to main content

SLC9

  • Reference work entry
  • First Online:
Encyclopedia of Signaling Molecules
  • 96 Accesses

Synonyms

Sodium/hydrogen exchanger; Solute carrier family 9

Historical Background

All living cells are critically dependent on homeostatic mechanisms that regulate intracellular pH, Na+ content, and, as a result, cell volume. Correspondingly, Na+ and H+ are among the most prevalent ions in living cells and are essential in cell bioenergetics. In 1974, West and Mitchell discovered sodium proton antiport activity in bacterial cells and suggested that Na+/H+ antiporter proteins have primary roles in the homeostasis of these cations (West and Mitchell 1974). Since then, sodium proton antiporters have been identified in the cytoplasmic and organelle membranes of almost all cells, including those of plants, animals and microorganisms. Furthermore, increasing numbers of these antiporters are being identified as human drug targets.

The SLC9 gene family encodes Na+/H+exchangers (NHEs) in many species from prokaryotes to eukaryotes. In humans, these proteins are associated with the...

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 4,499.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 4,499.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Bell SM, Schreiner CM, Schultheis PJ, Miller ML, Evans RL, Vorhees CV, et al. Targeted disruption of the murine Nhe1 locus induces ataxia, growth retardation, and seizures. Am J Phys. 1999;276:C788–95.

    Article  CAS  Google Scholar 

  • Christianson AL, Stevenson RE, van der Meyden CH, Pelser J, Theron FW, van Rensburg PL, et al. X linked severe mental retardation, craniofacial dysmorphology, epilepsy, ophthalmoplegia, and cerebellar atrophy in a large South African kindred is localised to Xq24-q27. J Med Genet. 1999;36:759–66.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Donowitz M, Ming Tse C, Fuster D. SLC9/NHE gene family, a plasma membrane and organellar family of Na(+)/H(+) exchangers. Mol Asp Med. 2013;34:236–51. doi:10.1016/j.mam.2012.05.001.

    Article  CAS  Google Scholar 

  • Garbern JY, Neumann M, Trojanowski JQ, Lee VM, Feldman G, Norris JW, et al. A mutation affecting the sodium/proton exchanger, SLC9A6, causes mental retardation with tau deposition. Brain. 2010;133:1391–402. doi:10.1093/brain/awq071.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gilfillan GD, Selmer KK, Roxrud I, Smith R, Kyllerman M, Eiklid K, et al. SLC9A6 mutations cause X-linked mental retardation, microcephaly, epilepsy, and ataxia, a phenotype mimicking Angelman syndrome. Am J Hum Genet. 2008;82:1003–10. doi:10.1016/j.ajhg.2008.01.013.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hunte C, Screpanti E, Venturi M, Rimon A, Padan E, Michel H. Structure of a Na+/H+ antiporter and insights into mechanism of action and regulation by pH. Nature. 2005;435:1197–202. doi:10.1038/nature03692.

    Article  PubMed  CAS  Google Scholar 

  • Kondapalli KC, Hack A, Schushan M, Landau M, Ben-Tal N, Rao R. Functional evaluation of autism-associated mutations in NHE9. Nat Commun. 2013;4:2510. doi:10.1038/ncomms3510.

    Article  PubMed  CAS  Google Scholar 

  • Landau M, Herz K, Padan E, Ben-Tal N. Model structure of the Na+/H+ exchanger 1 (NHE1) – functional and clinical implications. J Biol Chem. 2007;282:37854–63. doi:10.1074/jbc.M705460200.

    Article  PubMed  CAS  Google Scholar 

  • Milosavljevic N, Monet M, Lena I, Brau F, Lacas-Gervais S, Feliciangeli S, et al. The intracellular Na(+)/H(+) exchanger NHE7 effects a Na(+)-coupled, but not K(+)-coupled proton-loading mechanism in endocytosis. Cell Rep. 2014;7:689–96. doi:10.1016/j.celrep.2014.03.054.

    Article  PubMed  CAS  Google Scholar 

  • Morrow EM, Yoo SY, Flavell SW, Kim TK, Lin Y, Hill RS, et al. Identifying autism loci and genes by tracing recent shared ancestry. Science. 2008;321:218–23. doi:10.1126/science.1157657.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nygaard EB, Lagerstedt JO, Bjerre G, Shi B, Budamagunta M, Poulsen KA, et al. Structural modeling and electron paramagnetic resonance spectroscopy of the human Na+/H+ exchanger isoform 1, NHE1. J Biol Chem. 2011;286:634–48. doi:10.1074/jbc.M110.159202.

    Article  PubMed  CAS  Google Scholar 

  • Orlowski J, Grinstein S. Na+/H+ exchangers. Compr Physiol. 2011;1:2083–100. doi:10.1002/cphy.c110020.

    Article  PubMed  Google Scholar 

  • Padan E, Landau M. Sodium-Proton (Na+/H+) antiporters: properties and roles in health and disease. In: Sigel A, Sigel H, Sigel RKO, editors. The alkali metal ions: their role for life. Cham: Springer International Publishing; 2016. p. 391–458.

    Chapter  Google Scholar 

  • Schwede M, Garbett K, Mirnics K, Geschwind DH, Morrow EM. Genes for endosomal NHE6 and NHE9 are misregulated in autism brains. Mol Psychiatry. 2014;19:277–9. doi:10.1038/mp.2013.28.

    Article  PubMed  CAS  Google Scholar 

  • Slepkov ER, Rainey JK, Li X, Liu Y, Cheng FJ, Lindhout DA, et al. Structural and functional characterization of transmembrane segment IV of the NHE1 isoform of the Na+/H+ exchanger. J Biol Chem. 2005;280:17863–72.

    Article  PubMed  CAS  Google Scholar 

  • Stromme P, Dobrenis K, Sillitoe RV, Gulinello M, Ali NF, Davidson C, et al. X-linked Angelman-like syndrome caused by Slc9a6 knockout in mice exhibits evidence of endosomal-lysosomal dysfunction. Brain. 2011;134:3369–83. doi:10.1093/brain/awr250.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wakabayashi S, Pang T, Su X, Shigekawa M. A novel topology model of the human Na(+)/H(+) exchanger isoform 1. J Biol Chem. 2000;275:7942–9.

    Article  PubMed  CAS  Google Scholar 

  • Wakabayashi S, Hisamitsu T, Nakamura TY. Regulation of the cardiac Na(+)/H(+) exchanger in health and disease. J Mol Cell Cardiol. 2013;61:68–76. doi:10.1016/j.yjmcc.2013.02.007.

    Article  PubMed  CAS  Google Scholar 

  • West IC, Mitchell P. Proton/sodium ion antiport in Escherichia coli. Biochem J. 1974;144:87–90.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Meytal Landau .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Landau, M. (2018). SLC9. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101935

Download citation

Publish with us

Policies and ethics