Phosphorylation of RyR2 Ser‐2814 by CaMKII mediates β1‐adrenergic stress induced Ca 2+ ‐leak from the sarcoplasmic reticulum
| Autor: | Lars S. Maier, Mark Tilmann Seitz, Stefan Neef, Maria J. Baier, Jannis Noack |
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| Rok vydání: | 2021 |
| Předmět: |
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QH301-705.5 610 Medizin Adrenergic adrenergic stress 030204 cardiovascular system & hematology Ryanodine receptor 2 General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Adrenergic Agents 0302 clinical medicine Ca2+/calmodulin-dependent protein kinase SR Ca2+ leak Phosphorylation Biology (General) Research Articles 030304 developmental biology ddc:610 0303 health sciences CaMKII Chemistry Ryanodine receptor Endoplasmic reticulum Ryanodine Receptor Calcium Release Channel RyR2 Long-term potentiation Cell biology Sarcoplasmic Reticulum Calcium Ser‐2814 Calcium-Calmodulin-Dependent Protein Kinase Type 2 Research Article |
| Zdroj: | FEBS Open Bio, Vol 11, Iss 10, Pp 2756-2762 (2021) FEBS Open Bio |
| ISSN: | 2211-5463 |
| DOI: | 10.1002/2211-5463.13274 |
| Popis: | Adrenergic stimulation, while being the central mechanism of cardiac positive inotropy, is a universally acknowledged inductor of undesirable sarcoplasmic reticulum (SR) Ca2+ leak. However, the exact mechanisms for this remained unspecified so far. This study shows that Ca2+/calmodulin‐dependent protein kinase II (CaMKII)‐specific phosphorylation of ryanodine receptor type 2 at Ser‐2814 is the pivotal mechanism by which SR Ca2+ leak develops downstream of β1‐adrenergic stress by increase of the leak/load relationship. Cardiomyocytes with a Ser‐2814 phosphoresistant mutation (S2814A) were protected from isoproterenol‐induced SR Ca2+ leak and consequently displayed improved postrest potentiation of systolic Ca2+ release under adrenergic stress compared to littermate wild‐type cells. This study shows that Ca2+/calmodulin‐dependent protein kinase II‐specific phosphorylation of ryanodine receptor type 2 at Ser‐2814 is the pivotal mechanism by which sarcoplasmic reticulum Ca2+ leak develops downstream of β1‐adrenergic stress by increase of the leak/load relationship. |
| Databáze: | OpenAIRE |
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