2lt9

Structural highlights

Function

NAC3_MOUSE Mediates the electrogenic exchange of Ca(2+) against Na(+) ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellular processes. Contributes to cellular Ca(2+) homeostasis in excitable cells, both in muscle and in brain (PubMed:14722618, PubMed:21593315). In a first phase, voltage-gated channels mediate the rapid increase of cytoplasmic Ca(2+) levels due to release of Ca(2+) stores from the endoplasmic reticulum. SLC8A3 mediates the export of Ca(2+) from the cell during the next phase, so that cytoplasmic Ca(2+) levels rapidly return to baseline (PubMed:14722618, PubMed:21593315). Contributes to Ca(2+) transport during excitation-contraction coupling in muscle (PubMed:14722618). In neurons, contributes to the rapid decrease of cytoplasmic Ca(2+) levels back to baseline after neuronal activation, and thereby contributes to modulate synaptic plasticity, learning and memory (PubMed:21593315). Required for normal oligodendrocyte differentiation and for normal myelination (PubMed:21959935). Mediates Ca(2+) efflux from mitochondria and contributes to mitochondrial Ca(2+) ion homeostasis (PubMed:24616101). Isoform 1 displays higher calcium exchanger activity than isoform 2, probably because isoform 1 has a lower threshold for activation by cytoplasmic Ca(2+) (PubMed:24616101).^{[1] [2] [3] [4]}

References

1. ↑ Sokolow S, Manto M, Gailly P, Molgó J, Vandebrouck C, Vanderwinden JM, Herchuelz A, Schurmans S. Impaired neuromuscular transmission and skeletal muscle fiber necrosis in mice lacking Na/Ca exchanger 3. J Clin Invest. 2004 Jan;113(2):265-73. PMID:14722618 doi:10.1172/JCI18688
2. ↑ Molinaro P, Viggiano D, Nisticò R, Sirabella R, Secondo A, Boscia F, Pannaccione A, Scorziello A, Mehdawy B, Sokolow S, Herchuelz A, Di Renzo GF, Annunziato L. Na+ -Ca2+ exchanger (NCX3) knock-out mice display an impairment in hippocampal long-term potentiation and spatial learning and memory. J Neurosci. 2011 May 18;31(20):7312-21. PMID:21593315 doi:10.1523/JNEUROSCI.6296-10.2011
3. ↑ Boscia F, D'Avanzo C, Pannaccione A, Secondo A, Casamassa A, Formisano L, Guida N, Sokolow S, Herchuelz A, Annunziato L. Silencing or knocking out the Na(+)/Ca(2+) exchanger-3 (NCX3) impairs oligodendrocyte differentiation. Cell Death Differ. 2012 Apr;19(4):562-72. PMID:21959935 doi:10.1038/cdd.2011.125
4. ↑ Michel LYM, Verkaart S, Koopman WJH, Willems PHGM, Hoenderop JGJ, Bindels RJM. Function and regulation of the Na+-Ca2+ exchanger NCX3 splice variants in brain and skeletal muscle. J Biol Chem. 2014 Apr 18;289(16):11293-11303. PMID:24616101 doi:10.1074/jbc.M113.529388