ArticleJournal of molecular and cellular cardiology2017
Novel obscurins mediate cardiomyocyte adhesion and size via the PI3K/AKT/mTOR signaling pathway.
Article in Journal of molecular and cellular cardiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Using human induced pluripotent stem cell-derived cardiomyocytes to understand the mechanisms driving cardiomyocyte maturation.Frontiers in cardiovascular medicine · 2022Pooled it
- Obscurin a localizes near the cell membrane to modulate stress fiber dynamics and cell migration.The Journal of biological chemistry · 2026Article
- A Novel Germline Frameshift Variant in the Tumor Suppressor GeneInternational journal of molecular sciences · 2025Article
- The sodium/ascorbic acid co-transporter SVCT2 distributes in a striated membrane-enriched domain at the M-band level in slow-twitch skeletal muscle fibers.Biological research · 2024Article
- Essential role of obscurin kinase-1 in cardiomyocyte coupling via N-cadherin phosphorylation.JCI insight · 2024Article
- Effects and mechanisms of Salvia miltiorrhiza Bunge extract on myocardial cell apoptosis in rat heart failure model.Acta cirurgica brasileira · 2024Article
- Article
- Detecting Blood Methylation Signatures in Response to Childhood Cancer Radiotherapy via Machine Learning Methods.Biology · 2022Article
- Understanding the molecular basis of cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2022Review
- Cooperation of cell adhesion and autophagy in the brain: Functional roles in development and neurodegenerative disease.Matrix biology plus · 2021Review
- Obscurin: A multitasking giant in the fight against cancer.Biochimica et biophysica acta. Reviews on cancer · 2021Review
- Cyanocobalamin prevents cardiomyopathy in type 1 diabetes by modulating oxidative stress and DNMT-SOCS1/3-IGF-1 signaling.Communications biology · 2021Article
- The M-band: The underestimated part of the sarcomere.Biochimica et biophysica acta. Molecular cell research · 2020Review
- Intracellular calcium current disorder and disease phenotype inTheranostics · 2020Article
- Proteomic Analysis of Myocardia Containing the Obscurin R4344Q Mutation Linked to Hypertrophic Cardiomyopathy.Frontiers in physiology · 2020Article
- Patient mutations linked to arrhythmogenic cardiomyopathy enhance calpain-mediated desmoplakin degradation.JCI insight · 2019Article
- Supporting the heart: Functions of the cardiomyocyte's non-sarcomeric cytoskeleton.Journal of molecular and cellular cardiology · 2019Review
- Unraveling obscurins in heart disease.Pflugers Archiv : European journal of physiology · 2019Review
- Obscurin is a semi-flexible molecule in solution.Protein science : a publication of the Protein Society · 2019Article
- Murine obscurin and Obsl1 have functionally redundant roles in sarcolemmal integrity, sarcoplasmic reticulum organization, and muscle metabolism.Communications biology · 2019Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The intercalated disc of cardiac muscle embodies a highly-ordered, multifunctional network, essential for the synchronous contraction of the heart. Over 200 known proteins localize to the intercalated disc. The challenge now lies in their characterization as it relates to the coupling of neighboring cells and whole heart function. Using molecular, biochemical and imaging techniques, we characterized for the first time two small obscurin isoforms, obscurin-40 and obscurin-80, which are enriched at distinct locations of the intercalated disc. Both proteins bind specifically and directly to select phospholipids via their pleckstrin homology (PH) domain. Overexpression of either isoform or the PH-domain in cardiomyocytes results in decreased cell adhesion and size via reduced activation of the PI3K/AKT/mTOR pathway that is intimately linked to cardiac hypertrophy. In addition, obscurin-80 and obscurin-40 are significantly reduced in acute (myocardial infarction) and chronic (pressure overload) murine cardiac-stress models underscoring their key role in maintaining cardiac homeostasis. Our novel findings implicate small obscurins in the maintenance of cardiomyocyte size and coupling, and the development of heart failure by antagonizing the PI3K/AKT/mTOR pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.