| Nomikos, Michail, Thanassoulas, Angelos, Beck, Konrad, Vassilakopoulou, Vyronia, Hu, Handan, Calver, Brian Lewis, Theodoridou, Maria, Kashir, Junaid, Blayney, Lynda Mary, Livaniou, Evangelia, Rizkallah, Pierre, Nounesis, George and Lai, Francis Anthony 2014. Altered RyR2 regulation by the calmodulin F90L mutation associated with idiopathic ventricular fibrillation and early sudden cardiac death. Febs Letters 588 (17) , pp. 2898-2902. 10.1016/j.febslet.2014.07.007 |
Abstract
Calmodulin (CaM) association with the cardiac muscle ryanodine receptor (RyR2) regulates excitation–contraction coupling. Defective CaM–RyR2 interaction is associated with heart failure. A novel CaM mutation (CaMF90L) was recently identified in a family with idiopathic ventricular fibrillation (IVF) and early onset sudden cardiac death. We report the first biochemical characterization of CaMF90L. F90L confers a deleterious effect on protein stability. Ca2+-binding studies reveal reduced Ca2+-binding affinity and a loss of co-operativity. Moreover, CaMF90L displays reduced RyR2 interaction and defective modulation of [3H]ryanodine binding. Hence, dysregulation of RyR2-mediated Ca2+ release via aberrant CaMF90L–RyR2 interaction is a potential mechanism that underlies familial IVF.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Biosciences Dentistry Medicine |
| Subjects: | R Medicine > R Medicine (General) |
| Uncontrolled Keywords: | Calmodulin, Calcium, Ryanodine receptor, RyR2 calcium release channel, Idiopathic ventricular fibrillation, Sudden cardiac death. |
| Publisher: | Elsevier |
| ISSN: | 0014-5793 |
| Date of Acceptance: | 1 July 2014 |
| Last Modified: | 18 Jun 2019 19:46 |
| URI: | http://orca-mwe.cf.ac.uk/id/eprint/68577 |
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