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SLC8A3  -  solute carrier family 8 (sodium/calcium...

Homo sapiens

Synonyms: NCX3, Na(+)/Ca(2+)-exchange protein 3, Sodium/calcium exchanger 3, Solute carrier family 8 member 3
 
 
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Disease relevance of SLC8A3

 

High impact information on SLC8A3

  • Our findings indicate that NCX3 plays an important role in vivo in the control of Ca(2+) concentrations in the skeletal muscle fibers and at the neuromuscular junction [5].
  • The three Na+/Ca2+ exchanger isoforms, NCX1, NCX2, and NCX3, contain a large cytoplasmic loop that is responsible for the regulation of activity [6].
  • Working in the Ca(2+) efflux mode, Na(+)/Ca(2+) exchangers such as NCKX3 and NCX3 might, therefore, play a role in the Ag-induced mast cell activation by controlling the sustained phase of Ca(2+) mobilization [7].
  • Linkage analysis in the mouse indicated that the NCX family of genes is dispersed, since the NCX1, NCX2, and NCX3 genes mapped to mouse chromosomes 17, 7, and 12, respectively [8].
  • NCX3 was also expressed in the mammalian BHK cell line [8].
 

Biological context of SLC8A3

  • The human gene for member 3 of solute carrier family 8 (SLC8A3), encoding the Na+/Ca2+ exchanger isoform 3 (NCX3), was identified on chromosome 14q24 [9].
  • The human gene encoding the Na+/Ca2+ exchanger family member 3 (NCX3) undergoes extensive alternative splicing, with four variants previously identified [10].
  • NCX3-tN.2 consists of six exons including exon "a" and exons 4, 6, 7, 8 and 9 of NCX3, while NCX3-tN.1 lacks exon 4, but is otherwise similar to NCX3-tN [10].
  • Thus, the downregulation of the regulator of Ca2+ homeostasis NCX3 by Ca2+-regulated DREAM is a striking example of the autoregulatory property of the Ca2+ signal in neurons [11].
  • The NCX3 cDNA clone has an open reading frame of 2.8 kb encoding a protein of 927 amino acids [8].
 

Anatomical context of SLC8A3

  • Following addition of a poly(A)+ tail to the NCX3 clone, exchanger activity could be expressed in Xenopus oocytes [8].
  • In this study we investigated the time-related alteration of gene and protein expressions of NCX1, NCX2, and NCX3 in rat brain cortex after 2 h of transient middle cerebral artery occlusion (tMCAO) [12].
  • We compared the properties of three mammalian Na+/Ca2+ exchanger isoforms, NCX1, NCX2, and NCX3, by analyzing the effects of Ni2+ and other cations as well as the recently identified inhibitor isothiourea derivatives on intracellular Na+-dependent 45Ca2+ uptake into CCL-39 (Dede) fibroblasts stably expressing each isoform [13].
 

Associations of SLC8A3 with chemical compounds

  • To investigate which isoform was involved in [Ca2+]i increase and neuronal damage induced by A1254, we used specific antisense oligodeoxynucleotides (ODNs) to reduce NCX1 or NCX3 protein expression [14].
 

Analytical, diagnostic and therapeutic context of SLC8A3

References

  1. The human SLC8A3 gene and the tissue-specific Na+/Ca2+ exchanger 3 isoforms. Gabellini, N., Bortoluzzi, S., Danieli, G.A., Carafoli, E. Gene (2002) [Pubmed]
  2. Transcriptional regulation by cAMP and Ca2+ links the Na+/Ca2+ exchanger 3 to memory and sensory pathways. Gabellini, N. Mol. Neurobiol. (2004) [Pubmed]
  3. YM-244769, a Novel Na+/Ca2+ Exchange Inhibitor That Preferentially Inhibits NCX3, Efficiently Protects against Hypoxia/Reoxygenation-Induced SH-SY5Y Neuronal Cell Damage. Iwamoto, T., Kita, S. Mol. Pharmacol. (2006) [Pubmed]
  4. Na(+)/Ca(2+) exchange in human myotubes: intracellular calcium rises in response to external sodium depletion are enhanced in DMD. Deval, E., Levitsky, D.O., Marchand, E., Cantereau, A., Raymond, G., Cognard, C. Neuromuscul. Disord. (2002) [Pubmed]
  5. Impaired neuromuscular transmission and skeletal muscle fiber necrosis in mice lacking Na/Ca exchanger 3. Sokolow, S., Manto, M., Gailly, P., Molgó, J., Vandebrouck, C., Vanderwinden, J.M., Herchuelz, A., Schurmans, S. J. Clin. Invest. (2004) [Pubmed]
  6. Inhibitory interaction of the plasma membrane Na+/Ca2+ exchangers with the 14-3-3 proteins. Pulina, M.V., Rizzuto, R., Brini, M., Carafoli, E. J. Biol. Chem. (2006) [Pubmed]
  7. Modulation of Ca2+ signaling by Na+/Ca2+ exchangers in mast cells. Aneiros, E., Philipp, S., Lis, A., Freichel, M., Cavalié, A. J. Immunol. (2005) [Pubmed]
  8. Cloning of a third mammalian Na+-Ca2+ exchanger, NCX3. Nicoll, D.A., Quednau, B.D., Qui, Z., Xia, Y.R., Lusis, A.J., Philipson, K.D. J. Biol. Chem. (1996) [Pubmed]
  9. Control of the Na+/Ca2+ exchanger 3 promoter by cyclic adenosine monophosphate and Ca2+ in differentiating neurons. Gabellini, N., Bortoluzzi, S., Danieli, G.A., Carafoli, E. J. Neurochem. (2003) [Pubmed]
  10. Molecular cloning and characterization of two novel truncated isoforms of human Na+/Ca2+ exchanger 3, expressed in fetal brain. Lindgren, R.M., Zhao, J., Heller, S., Berglind, H., Nistér, M. Gene (2005) [Pubmed]
  11. Downstream regulatory element antagonist modulator regulates Ca2+ homeostasis and viability in cerebellar neurons. Gomez-Villafuertes, R., Torres, B., Barrio, J., Savignac, M., Gabellini, N., Rizzato, F., Pintado, B., Gutierrez-Adan, A., Mellström, B., Carafoli, E., Naranjo, J.R. J. Neurosci. (2005) [Pubmed]
  12. Selective alteration of expression of Na+/Ca2+ exchanger isoforms after transient focal cerebral ischemia in rats. Li, L.L., Sun, L.N., Zhou, H.Y., Li, Z.B., Wang, X.L. Neurosci. Lett. (2006) [Pubmed]
  13. Differential inhibition of Na+/Ca2+ exchanger isoforms by divalent cations and isothiourea derivative. Iwamoto, T., Shigekawa, M. Am. J. Physiol. (1998) [Pubmed]
  14. Involvement of Na+-Ca2+ exchanger in intracellular Ca2+ increase and neuronal injury induced by polychlorinated biphenyls in human neuroblastoma SH-SY5Y cells. Magi, S., Castaldo, P., Carrieri, G., Scorziello, A., Di Renzo, G., Amoroso, S. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
 
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