Abstract
The Na(+)-Ca(2+) exchanger (NCX) mediated Ca(2+) fluxes are essential for handling Ca(2+) homeostasis in many cell-types. Eukaryotic NCX variants contain regulatory CBD1 and CBD2 domains, whereas in distinct variants the Ca(2+) binding to Ca3-Ca4 sites of CBD1 results either in sustained activation, inhibition or no effect. CBD2 contains an alternatively spliced segment, which is expressed in a tissue-specific manner although its impact on allosteric regulation remains unclear. Recent studies revealed that the Ca(2+) binding to Ca3-Ca4 sites results in interdomain tethering of CBDs, which rigidifies CBDs movements with accompanied slow dissociation of "occluded" Ca(2+). Here we investigate the effects of CBD2 variants on Ca(2+) occlusion in the two-domain construct (CBD12). Mutational studies revealed that both sites (Ca3 and Ca4) contribute to Ca(2+) occlusion, whereas after dissociation of the first Ca(2+) ion the second Ca(2+) ion becomes occluded. This mechanism is common for the brain, kidney and cardiac splice variants of CBD12, although the occluded Ca(2+) exhibits 20-50-fold difference in off-rates among the tested variants. Therefore, the spliced exons on CBD2 affect the rate-limiting step of the occluded Ca(2+) dissoc...Continue Reading
References
Dec 1, 1992·The Journal of General Physiology·D W HilgemannA Collins
Dec 1, 1992·The Journal of General Physiology·D W HilgemannS Matsuoka
Mar 1, 1995·The Journal of General Physiology·S MatsuokaK D Philipson
May 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·S MatsuokaK D Philipson
Jul 1, 1996·The Journal of General Physiology·L V HryshkoK D Philipson
Dec 14, 1999·The Journal of General Physiology·C DyckL V Hryshko
May 8, 2003·Pflügers Archiv : European journal of physiology·Beate D QuednauKenneth D Philipson
May 28, 2004·Molecular Biology and Evolution·Xinjiang Cai, Jonathan Lytton
Dec 17, 2004·Pharmacological Reviews·L AnnunziatoG F Di Renzo
Apr 8, 2006·Molecular Cell·Mark HilgeGeerten W Vuister
Jun 16, 2006·The Journal of Biological Chemistry·Debora A NicollJeff Abramson
Aug 25, 2007·The Biochemical Journal·Jonathan Lytton
Oct 27, 2007·Proceedings of the National Academy of Sciences of the United States of America·Gabriel Mercado BessererJeff Abramson
Jan 15, 2009·The Journal of Biological Chemistry·Liron BoymanDaniel Khananshvili
Apr 1, 2009·The Journal of Biological Chemistry·Vincent ChaptalJeff Abramson
Apr 14, 2009·Journal of Molecular Biology·Mousheng WuLei Zheng
Aug 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Mark HilgeGeerten W Vuister
Oct 6, 2009·The Journal of Biological Chemistry·Michela OttoliaKenneth D Philipson
Oct 10, 2009·The Journal of Biological Chemistry·Mousheng WuLei Zheng
Jul 1, 2010·The Journal of Biological Chemistry·Moshe GiladiDaniel Khananshvili
Jan 7, 2011·Proceedings of the National Academy of Sciences of the United States of America·Scott A JohnMichela Ottolia
Jun 18, 2011·The Journal of Biological Chemistry·Liron BoymanDaniel Khananshvili
Jul 23, 2011·The Journal of Biological Chemistry·Roberto K SalinasRafael Brüschweiler
Oct 18, 2011·Structure·Mousheng WuLei Zheng
Feb 11, 2012·Science·Jun LiaoYouxing Jiang
Citations
Nov 28, 2013·Pflügers Archiv : European journal of physiology·Daniel Khananshvili
Sep 15, 2014·Cell Calcium·Lior AlmagorDaniel Khananshvili
Nov 13, 2015·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Raimond L WinslowJoseph L Greenstein
Feb 24, 2016·Frontiers in Physiology·Moshe GiladiDaniel Khananshvili
Nov 13, 2014·The Biochemical Journal·Moshe GiladiDaniel Khananshvili
Sep 3, 2013·Journal of Molecular Biology·Moshe GiladiJoel A Hirsch
Feb 7, 2016·Proteins·Layara Akemi AbikoRafael Brüschweiler
Mar 1, 2016·Cell Calcium·Inbal TalDaniel Khananshvili
Jul 6, 2016·Journal of Molecular and Cellular Cardiology·Lulu ChuRaimond L Winslow
Aug 29, 2012·Biochemistry·Moshe GiladiDaniel Khananshvili
Jun 27, 2013·The Journal of Biological Chemistry·Moshe GiladiDaniel Khananshvili
Dec 9, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Su Youn LeeDaniel Khananshvili
Jan 14, 2020·Neurochemical Research·Samantha A SpencerBabette Fuss
Dec 7, 2017·Experimental Physiology·Alexei VerkhratskyIsrael Sekler
Apr 22, 2017·Scientific Reports·Moshe GiladiDaniel Khananshvili
Dec 4, 2019·Cell Calcium·Daniel Khananshvili
May 30, 2021·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·Mel V BooYuen K Ip
Jun 24, 2020·Biophysical Journal·Marcus V C CardosoRoberto K Salinas
Jul 27, 2021·Biophysical Journal·Maximilia F de Souza DegenhardtRoberto K Salinas