Abstract 15023: Junctophilin-2 (JPH2) Interactome in Ventricular Myocytes is Subcellular Compartment-dependent and Subject to Remodeling During Hypertrophy Leading to Heart Failure
| العنوان: | Abstract 15023: Junctophilin-2 (JPH2) Interactome in Ventricular Myocytes is Subcellular Compartment-dependent and Subject to Remodeling During Hypertrophy Leading to Heart Failure |
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| المؤلفون: | Wilson T Zachary, Gea-Ny Tseng, Min Jiang, Tytus Bernas, Soltisz Andrew, Rengasayee Veeraraghavan |
| المصدر: | Circulation. 142 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Cell physiology, Sarcolemma, business.industry, Endoplasmic reticulum, medicine.disease, Interactome, Cell biology, Muscle hypertrophy, Contractility, Physiology (medical), Heart failure, JPH2, medicine, Cardiology and Cardiovascular Medicine, business |
| الوصف: | Introduction: Junctions between sarco/endoplasmic reticulum (SR/ER) and sarcolemma (SL), where Ca-induced Ca release (CICR) takes place, are important for myocardial contractility. JPH2 is the major SR/SL tether in cardiomyocytes. Hypothesis: JPH2 interacts with diverse proteins depending on its subcellular location. Furthermore, JPH2's distribution and relations with its interactors are subject to remodeling in diseased state. Methods: We studied spontaneously hypertensive rats: 2-3 months (SY, healthy) and ≥ 20 months (SO, in heart failure). We used immunoprecipitation (IP) and global unbiased search (proteomics) to identify JPH2's interactors in cardiomyocytes. We used high-resolution structured illumination microscopy (SIM) followed by deconvolution and object-based segmentation in 3 dimension (OBS3D) to quantify spatial relationships between JPH2 and interactors. Results: Based on proteomics JPH2's interactors are involved in: SR/ER function, vesicular transport, sub-sarcolemma scaffold, ion transporters/channels, intercalated disc (ICD) organization and mitochondrial function. We quantified spatial relationships between JPH2 and 6 interactors representing distinct subcellular compartments: RyR2 (junctional SR), Cav1.2 (t-tubules), dystrophin (peripheral SL), caveolin-3 (caveolae), connexin-43 (ICD), and prohibitin-1 (mitochondria). In SY myocytes, JPH2 clusters are organized along the z-lines and peripheral SL, consistent with close and reciprocal association in JPH2/RyR2 and JPH2/dystrophin. In SO myocytes, JPH2 is dispersed from z-lines but stays close to peripheral SL and clusters to ICD. This leads to reduced proximity between JPH2 and Cav1.2 or RyR2, but closer proximity to connexin-43. Conclusions: In failing heart, a portion of JPH2 shifts from t-tubule/SR junctions (where CICR occurs) to ICDs (where store-operated Ca entry 'SOCE' occurs), likely contributing to dysregulation of intracellular Ca handling. |
| تدمد: | 1524-4539 0009-7322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::52192df93de984e22f09e0016bc73293 https://doi.org/10.1161/circ.142.suppl_3.15023 |
| رقم الأكسشن: | edsair.doi...........52192df93de984e22f09e0016bc73293 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244539 00097322 |
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