ArticleNature communications2022
Tmem65 is critical for the structure and function of the intercalated discs in mouse hearts.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Dysferlin stabilizes membrane nanodomains of cardiomyocytes after myocardial infarction.Scientific reports · 2026Article
- Subcellular Proteomic Analyses Reveal REEP5 Knockdown in the Mouse Heart Disrupts Mitochondrial Networks.Molecular & cellular proteomics : MCP · 2026Article
- Genomic structural equation modeling reveals shared genetic structure of cardiac function and structure-function association studies of CLCNKA mutations.Scientific reports · 2026Article
- Mitochondrial Adaptation to Mechanical Stress in Cardiac Ageing and Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- TMEM65-dependent Ca2+ extrusion safeguards mitochondrial homeostasis.Nature communications · 2025Article
- Calcium Signaling and Cardiac Adaptation to Stress: Focus on Pregnancy and Diabetes.Biomolecules · 2025Review
- MYC/TET3-Regulated TMEM65 Activates OXPHOS-SERPINB3 Pathway to Promote Progression and Cisplatin Resistance in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Glyoxal is a superior fixative to formaldehyde in promoting antigenicity and structural integrity in murine cardiac tissues.Journal of molecular and cellular cardiology plus · 2025Article
- Distribution characteristics and morphological comparison of telocytes in the aortic bulb and myocardium of yak heart.BMC veterinary research · 2025Article
- Genetic Risk of Different Populations in COVID-19 Susceptibility and Severity.Infection and drug resistance · 2025Review
- New focus on cardiac voltage-gated sodium channel β1 and β1B: Novel targets for treating and understanding arrhythmias?Heart rhythm · 2025Review
- Progressive cardiomyopathy with intercalated disc disorganization in a rat model of Becker dystrophy.EMBO reports · 2024Article
- Development and characterization of the mode-of-action of inhibitory and agonist peptides targeting the voltage-gated sodium channel SCN1B beta-subunit.Journal of molecular and cellular cardiology · 2024Article
- Low-intensity exercise training improves systolic function of heart during metastatic melanoma-induced cachexia in mice.Heliyon · 2024Article
- The intercalated disc: a unique organelle for electromechanical synchrony in cardiomyocytes.Physiological reviews · 2023Review
- Proteomics and phosphoproteomics of failing human left ventricle identifies dilated cardiomyopathy-associated phosphorylation of CTNNA3.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 2 countries.
Funding
Abstract
The intercalated disc (ICD) is a unique membrane structure that is indispensable to normal heart function, yet its structural organization is not completely understood. Previously, we showed that the ICD-bound transmembrane protein 65 (Tmem65) was required for connexin43 (Cx43) localization and function in cultured mouse neonatal cardiomyocytes. Here, we investigate the functional and cellular effects of Tmem65 reductions on the myocardium in a mouse model by injecting CD1 mouse pups (3-7 days after birth) with recombinant adeno-associated virus 9 (rAAV9) harboring Tmem65 shRNA, which reduces Tmem65 expression by 90% in mouse ventricles compared to scrambled shRNA injection. Tmem65 knockdown (KD) results in increased mortality which is accompanied by eccentric hypertrophic cardiomyopathy within 3 weeks of injection and progression to dilated cardiomyopathy with severe cardiac fibrosis by 7 weeks post-injection. Tmem65 KD hearts display depressed hemodynamics as measured echocardiographically as well as slowed conduction in optical recording accompanied by prolonged PR intervals and QRS duration in electrocardiograms. Immunoprecipitation and super-resolution microscopy demonstrate a physical interaction between Tmem65 and sodium channel β subunit (β1) in mouse hearts and this interaction appears to be required for both the establishment of perinexal nanodomain structure and the localization of both voltage-gated sodium channel 1.5 (NaV1.5) and Cx43 to ICDs. Despite the loss of NaV1.5 at ICDs, whole-cell patch clamp electrophysiology did not reveal reductions in Na
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