Activation of the cardiac Na(+)-Ca(2+) exchanger by sorcin via the interaction of the respective Ca(2+)-binding domains.
Bottom Line: To investigate the importance of this region in the interaction with NCX1, three variants were examined: W105G and W99G, mutated respectively near EF3 and EF2, and E124A that does not bind Ca(2+) due to a mutation at EF3.Downregulation of sorcin decreased and supplementation with wt sorcin (3muM) increased NCX activity in isolated cardiomyocytes.The relative stimulatory effects of the sorcin variants were: W105G>wt sorcin>Sorcin Calcium Binding Domain (SCBD)>W99G>E124A.
Affiliation: C.N.R. Institute of Molecular Biology and Pathology, Department of Biochemical Sciences A. Rossi Fanelli, Sapienza University of Rome, 00185 Rome, Italy. firstname.lastname@example.orgShow MeSH
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Mentions: The presence of 3 μM sorcin Ca2+-binding domain (SCBD) increases NCX activity by about 120% relative to control suggesting this domain is important in the stimulation of NCX1 activity, in accord with its involvement in formation of the sorcin–NCX1 complex (Fig. 7). The different sorcin variants analyzed have strikingly different effects on the activity of NCX1 as already observed in the case of the Ca2+ spark properties which reflect RyR2 activity in cardiomyocytes [33,34]. This applies in particular to the W99G and W105G variants which carry a mutation in the D helix at a distance of only two helical turns. The W105G variant quadruplicates NCX activity with respect to control and therefore resembles wt sorcin (Fig. 3), whereas W99G increases the Ni2+-sensitive currents by about 60% with respect to control. The E124A mutant, characterized by impaired binding of Ca2+ to the highest affinity EF3 site, is indistinguishable from control.
Affiliation: C.N.R. Institute of Molecular Biology and Pathology, Department of Biochemical Sciences A. Rossi Fanelli, Sapienza University of Rome, 00185 Rome, Italy. email@example.com