scholarly journals Understanding How Phosphorylation and Redox Modifications Regulate Cardiac Ryanodine Receptor Type 2 Activity to Produce an Arrhythmogenic Phenotype in Advanced Heart Failure

2020 ◽  
Vol 3 (4) ◽  
pp. 563-582
Author(s):  
Alexander Dashwood ◽  
Elizabeth Cheesman ◽  
Nicole Beard ◽  
Haris Haqqani ◽  
Yee Weng Wong ◽  
...  
2020 ◽  
Author(s):  
Tianxia Luo ◽  
Ningning Yan ◽  
Mengru Xu ◽  
Fengjuan Dong ◽  
Qian Liang ◽  
...  

Abstract Background: Ryanodine receptor type 2 (RyR2) mediate Ca 2+ release from the endoplasmic and sarcoplasmic reticulum (ER and SR), which is involved in the peripheral coupling of mouse cardiomyocytes, and thereby plays an important role in cardiac contraction. Junctophilin-2 (JPH2, JP2) is anchored to the plasma membrane (PM) and membranes of the ER and SR, and modulates intracellular Ca 2+ handling through regulation of RyR2. However, the potential RyR2 binding region of JPH2 is poorly understood. Methods: The interaction of JPH2 with RyR2 was studied using LC-MS/MS , bioinformatic analysis,co-immunoprecipitation studies in cardiac SR vesicles. GST-pull down analysis was performed to investigate the physical interaction between RyR2 and JPH2 fragments. Immunofluorescent staining was carried out to determine the colocalization of RyR2 and JPH2 in isolated mouse cardiomyocytes. Ion Optix photometry system was used to measure the levels of intracellular Ca 2+ transients in cardiomyocytes isolated from JPH2 knock down mice. Results: We report that (i) JPH2 interacts with RyR2 and (ii) the C terminus of the JPH2 protein can pull down RyR2 receptors. Confocal immunofluorescence imaging indicated that the majority of JPH2 and RyR2 proteins were colocalized near Z-lines. A decrease in the levels of JPH2 expression reduced the amplitude of Ca 2+ transients in cardiomyocytes. Conclusions: This study suggests that the C terminus domain of JPH2 is required for interactions with RyR2 in the context of peripheral coupling of mouse cardiomyocytes, which provide a molecular mechanism for looking for Ca 2+ - related diseases prevention strategies.


2015 ◽  
Vol 66 (16) ◽  
pp. C57-C58
Author(s):  
Kangyin Chen ◽  
Tigang Huang ◽  
Tong Liu ◽  
Yong-Jian Li ◽  
Xin Zhou ◽  
...  

Cell Calcium ◽  
2003 ◽  
Vol 34 (3) ◽  
pp. 261-269 ◽  
Author(s):  
Jens H Westhoff ◽  
Sung-Yong Hwang ◽  
R Scott Duncan ◽  
Fumiko Ozawa ◽  
Pompeo Volpe ◽  
...  

2011 ◽  
Vol 17 (8) ◽  
pp. S13
Author(s):  
Jonathan L. Respress ◽  
Ralph J. van Oort ◽  
Angela C. de Almeida ◽  
Na Li ◽  
Natale Rolim ◽  
...  

Hypertension ◽  
2011 ◽  
Vol 58 (6) ◽  
pp. 1099-1110 ◽  
Author(s):  
Yunzeng Zou ◽  
Yanyan Liang ◽  
Hui Gong ◽  
Ning Zhou ◽  
Hong Ma ◽  
...  

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