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Slc9a4  -  solute carrier family 9, subfamily A (NHE4...

Rattus norvegicus

Synonyms: NHE-4, Na(+)/H(+) exchanger 4, Nhe4, Sodium/hydrogen exchanger 4, Solute carrier family 9 member 4
 
 
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High impact information on Slc9a4

  • Overall, the protein exhibits 47.8%, 41.2%, and 56.2% amino acid sequence identity to NHE-1, NHE-3, and NHE-4, respectively [1].
  • NHE-4 mRNA is most abundant in stomach, followed by intermediate levels in small intestine and colon and lesser amounts in kidney, brain, uterus, and skeletal muscle [2].
  • There was no expression of NHE-2, NHE-3, or NHE-4 in SHR and WKY aortas or in cultured vascular smooth muscle cells from SHR and WKY aortas [3].
  • In the present work, we investigated whether alterations in the steady-state levels of specific Na(+)-H+ exchanger mRNA isoforms (NHE-1 through NHE-4) are associated with the observed increases in exchanger activity [3].
  • The results indicate that NHE4 is highly expressed in basolateral membranes of thick ascending limb and distal convoluted tubule, whereas collecting ducts from cortex to inner medulla and proximal tubules showed weaker basolateral NHE4 expression [4].
 

Biological context of Slc9a4

  • The Na+/H+ exchanger NHE4 was cloned from a rat stomach cDNA library and shown to be expressed predominantly in the stomach and less dramatically in the kidney [4].
  • When induced by cell shrinkage, NHE4 exhibits a sigmoidal response to increasing extracellular Na+ concentrations, suggesting allosteric or cooperative binding kinetics [5].
  • Tissue distribution of Na+/H+ exchanger isoforms NHE2 and NHE4 in rat intestine and kidney [6].
  • NHE2 is likely involved in gut Na+ absorption, whereas NHE4 may have a specialized role in cell volume rectification of inner medullary collecting duct cells [6].
 

Anatomical context of Slc9a4

  • Immunolocalization of anion exchanger AE2, Na(+)/H(+) exchangers NHE1 and NHE4, and vacuolar type H(+)-ATPase in rat pancreas [7].
  • Therefore, we propose that NHE1 and NHE4 are expressed in zymogen granule membranes of rat exocrine pancreas [8].
  • Immunoblotting of plasma membranes with transporter-specific antibodies revealed protein bands at approximately 160 kD for AE2, at approximately 90 kD and approximately 103 kD for NHE1 and NHE4, respectively, and at 31 kD and 70 kD for V-ATPase [7].
  • Amiloride inhibited weakly suggesting that "amiloride-resistant" and "amiloride-sensitive" NHE are expressed in zymogen granules. cDNA sequences encoding NHE1- and NHE4-specific transmembrane domains were detected by RT-PCR in rat pancreatic tissue and in the rat pancreatic acinar cell line AR4-2J [8].
  • Characterization of the rat Na+/H+ exchanger isoform NHE4 and localization in rat hippocampus [5].
 

Associations of Slc9a4 with chemical compounds

 

Analytical, diagnostic and therapeutic context of Slc9a4

  • A polyclonal antibody against a unique NHE4 decapeptide was used for immunohistochemistry in rat kidney [4].
  • Western blot analysis of NHE4 in membrane fractions prepared from the inner stripe of the outer medulla revealed the presence of a 95-kDa protein that was enriched in basolateral membrane vesicles isolated from medullary thick ascending limbs [4].
  • Cortical NHE-1 increased mildly at 12 and 24 hours of reperfusion whereas a moderate decrease in NHE-2 and NHE-4 mRNAs was observed in cortex and medulla after both 12 and 24 hours of reperfusion [10].
  • NHE1 and NHE4 were further identified by amplification of isoform-specific cDNA using RT-PCR [7].
  • The Cl(-)/HCO(3)(-) exchanger AE2, the Na(+)/H(+) exchangers NHE1 and NHE4, and the 31-kD and 70-kD vacuolar H(+)-ATPase (V-ATPase) subunits were detected by immunoblotting and immunocytochemical techniques [7].

References

  1. Molecular cloning, sequencing, tissue distribution, and functional expression of a Na+/H+ exchanger (NHE-2). Collins, J.F., Honda, T., Knobel, S., Bulus, N.M., Conary, J., DuBois, R., Ghishan, F.K. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  2. Molecular cloning of putative members of the Na/H exchanger gene family. cDNA cloning, deduced amino acid sequence, and mRNA tissue expression of the rat Na/H exchanger NHE-1 and two structurally related proteins. Orlowski, J., Kandasamy, R.A., Shull, G.E. J. Biol. Chem. (1992) [Pubmed]
  3. Na(+)-H+ exchanger expression in vascular smooth muscle of spontaneously hypertensive and Wistar-Kyoto rats. Lucchesi, P.A., DeRoux, N., Berk, B.C. Hypertension (1994) [Pubmed]
  4. Localization and functional characterization of Na+/H+ exchanger isoform NHE4 in rat thick ascending limbs. Chambrey, R., St John, P.L., Eladari, D., Quentin, F., Warnock, D.G., Abrahamson, D.R., Podevin, R.A., Paillard, M. Am. J. Physiol. Renal Physiol. (2001) [Pubmed]
  5. Characterization of the rat Na+/H+ exchanger isoform NHE4 and localization in rat hippocampus. Bookstein, C., Musch, M.W., DePaoli, A., Xie, Y., Rabenau, K., Villereal, M., Rao, M.C., Chang, E.B. Am. J. Physiol. (1996) [Pubmed]
  6. Tissue distribution of Na+/H+ exchanger isoforms NHE2 and NHE4 in rat intestine and kidney. Bookstein, C., Xie, Y., Rabenau, K., Musch, M.W., McSwine, R.L., Rao, M.C., Chang, E.B. Am. J. Physiol. (1997) [Pubmed]
  7. Immunolocalization of anion exchanger AE2, Na(+)/H(+) exchangers NHE1 and NHE4, and vacuolar type H(+)-ATPase in rat pancreas. Roussa, E., Alper, S.L., Thévenod, F. J. Histochem. Cytochem. (2001) [Pubmed]
  8. Expression of NHE1 and NHE4 in rat pancreatic zymogen granule membranes. Anderie, I., Blum, R., Haase, W., Grinstein, S., Thévenod, F. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  9. Heterologous expression of rat NHE4: a highly amiloride-resistant Na+/H+ exchanger isoform. Chambrey, R., Achard, J.M., Warnock, D.G. Am. J. Physiol. (1997) [Pubmed]
  10. Ischemic-reperfusion injury in the kidney: overexpression of colonic H+-K+-ATPase and suppression of NHE-3. Wang, Z., Rabb, H., Craig, T., Burnham, C., Shull, G.E., Soleimani, M. Kidney Int. (1997) [Pubmed]
 
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