JPH2 Antibody
Description
Introduction to JPH2 Antibody
JPH2 Antibody is a polyclonal antibody (e.g., ab79071 from Abcam) that specifically binds to Junctophilin-2, a protein encoded by the JPH2 gene. JPH2 is essential for forming junctional membrane complexes (JMCs) in cardiac and smooth muscle cells, facilitating communication between plasma membrane ion channels (e.g., L-type calcium channels) and sarcoplasmic reticulum (SR) proteins like ryanodine receptors (RyR2) . The antibody is widely used in Western blot (WB), ELISA, and immunohistochemistry to study JPH2’s expression, localization, and interactions.
Development and Validation
The JPH2 antibody (ab79071) is generated using a synthetic peptide immunogen corresponding to a region within human JPH2. Key validation data include:
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Applications: Validated for WB (1–2 µg/mL dilution) and ELISA .
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Band Specificity: Detects bands at 64 kDa and 74 kDa in mouse brain lysate, aligning with predicted JPH2 isoforms .
Research Applications
JPH2 antibodies have been instrumental in:
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Cardiac Dyad Studies: Visualizing JPH2’s role in tethering SR and plasma membranes to enable calcium-induced calcium release (CICR) .
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Smooth Muscle Research: Demonstrating JPH2’s necessity for coupling RyR2 clusters with BK channels in cerebral arteries .
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Disease Mechanisms: Investigating mutations in JPH2 linked to cardiomyopathy and Huntington’s disease-like 2 .
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Mitochondrial Studies: Revealing JPH2’s interaction with MFN2 to regulate mitochondrial metabolism in cardiomyocytes .
Disease Associations
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Over 80 cardiomyopathy-linked mutations in JPH2 destabilize its interactions with ion channels or alter dyad structure .
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Calpain-mediated JPH2 cleavage during heart failure disrupts T-tubule integrity, a process detectable using JPH2 antibodies .
Mitochondrial Regulation
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JPH2 co-localizes with MFN2 in mitochondria, and its knockout in iPSC-derived cardiomyocytes reduces oxygen consumption rates and mitochondrial mass .
Clinical Implications
JPH2 antibodies aid in diagnosing and studying:
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Cardiac Hypertrophy: Reduced JPH2 expression correlates with dyad disruption and impaired calcium handling .
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Therapeutic Targets: Calpain inhibitors preserve JPH2 integrity, preventing T-tubule remodeling in heart failure models .
Limitations and Future Directions
While JPH2 antibodies are critical for basic research, challenges include:
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Cross-Reactivity: Potential detection of cleavage fragments (e.g., nuclear-localized N-terminal fragments) .
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Model Systems: Most studies rely on murine models; human tissue validation remains limited .
Future studies could leverage advanced imaging (e.g., superresolution microscopy) to map JPH2 nanodomains in diseased tissues .
Product Specs
Target Background
Junctophilin-2 (JP2) is a membrane-binding protein crucial for excitation-contraction coupling in cardiomyocytes. It forms a structural link between the plasma membrane and the sarcoplasmic reticulum, maintaining the critical 12-15 nm gap between these membranes in cardiac dyads. This structural role is essential for proper intracellular calcium (Ca2+) signaling, facilitating ryanodine receptor-mediated Ca2+ release. JP2 also contributes to the formation of skeletal muscle triad junctions. Furthermore, JP2 acts as a transcriptional repressor, protecting against the detrimental effects of cardiac stress. Upon cardiac stress, calpain cleaves JP2, releasing a fragment that translocates to the nucleus. Here, it represses genes involved in cell growth, differentiation, hypertrophy, inflammation, and fibrosis, thereby mitigating pathological remodeling.
- A novel JPH2 mutation has been linked to dilated cardiomyopathy (PMID: 27471098).
- Calpain cleaves JP2 at multiple sites, generating dysfunctional truncations (PMID: 26063807).
- Microtubule densification and T-tubule remodeling are mechanistically linked, with microtubule-mediated JP2 redistribution contributing to T-tubule disruption, impaired excitation-contraction coupling, and heart failure (PMID: 24519927).
- The S101R mutation may affect JP2 dyad organization and alter JP2 protein interactions that regulate calcium cycling (PMID: 24001019).
- A JPH2 mutant (Y141H) induces hypertrophy in skeletal myotubes by increasing store-operated Ca2+ entry via Orai1 (PMID: 22389502).
- Loss-of-function JPH2 mutations cause cardiac-specific JP2 deficiency, leading to impaired contractility, heart failure, and increased mortality (PMID: 21339484).
- Reduced JP2 expression in patients with hypertrophic cardiomyopathy results in decreased excitation-contraction coupling gain and altered Ca2+ homeostasis, potentially contributing to prohypertrophic remodeling (PMID: 21216834).
- The S165F mutation in JP2 affects Ca2+ signaling in skeletal muscle (PMID: 20095964).
- JPH2 mutations have been associated with hypertrophic cardiomyopathy (PMID: 17476457, PMID: 17509612).
