ArticleCirculation research2023
Interaction of Filamin C With Actin Is Essential for Cardiac Development and Function.
Article in Circulation research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Filamin C activates MAPK/ERK signaling to facilitate epithelial-mesenchymal transition in bladder cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- A narrow developmental window defines PKN2's essential role in ventricular chamber morphogenesis.Communications biology · 2026Article
- Transcriptional readthrough at Atf4 locus suppresses Rps19bp1 and impairs heart development.Cardiovascular research · 2026Article
- Genetic Architecture of N-Terminal Pro-B-Type Natriuretic Peptide in a Multiancestry Study Population.Circulation. Genomic and precision medicine · 2026Article
- Article
- Identification of a NovelDiagnostics (Basel, Switzerland) · 2025Article
- In Vivo Models of Cardiovascular Disease:Biomedicines · 2025Review
- Tailored therapeutics for cardiomyopathies.Nature reviews. Cardiology · 2025Review
- Transcriptional Readthrough atbioRxiv : the preprint server for biology · 2025Article
- Transcriptomic profiling of skeletal muscle in the DMDScientific reports · 2025Article
- Unveiling the multifaceted role of the FLNC gene: implications for cancer diagnosis and prognosis.European journal of medical research · 2025Article
- Spatial transcriptomics and multi-omics reveal relapse and resistance mechanisms of EndMT-derived CAFs mediated by TNC and FLNC in glioblastoma.Journal of translational medicine · 2025Article
- Quantitative Proteomics Revealed the Molecular Regulatory Network of Lysine and the Effects of Lysine Supplementation on Sunit Skeletal Muscle Satellite Cells.Animals : an open access journal from MDPI · 2025Article
- α Protein Kinase 3 Is Essential for Neonatal and Adult Cardiac Function.Journal of the American Heart Association · 2025Article
- Mutations in Filamin C Associated with Both Alleles Do Not Affect the Functioning of Mice Cardiac Muscles.International journal of molecular sciences · 2025Article
- The Role of Signalling Pathways in Myocardial Fibrosis in Hypertrophic Cardiomyopathy.Reviews in cardiovascular medicine · 2025Review
- Article
- Identification of a Missense Mutation in theJournal of multidisciplinary healthcare · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundFLNC (filamin C), a member of the filamin family predominantly expressed in striated muscles, plays a crucial role in bridging the cytoskeleton and ECM (extracellular matrix) in cardiomyocytes, thereby maintaining heart integrity and function. Although genetic variants within the N-terminal ABD (actin-binding domain) of FLNC have been identified in patients with cardiomyopathy, the precise contribution of the actin-binding capability to FLNC's function in mammalian hearts remains poorly understood.
methodsWe conducted in silico analysis of the 3-dimensional structure of mouse FLNC to identify key amino acid residues within the ABD that are essential for FLNC's actin-binding capacity. Subsequently, we performed coimmunoprecipitation and immunofluorescent assays to validate the in silico findings and assess the impact of these mutations on the interactions with other binding partners and the subcellular localization of FLNC. Additionally, we generated and analyzed knock-in mouse models in which the FLNC-actin interaction was completely disrupted by these mutations.
resultsOur findings revealed that F93A/L98E mutations completely disrupted FLNC-actin interaction while preserving FLNC's ability to interact with other binding partners ITGB1 (β1 integrin) and γ-SAG (γ-sarcoglycan), as well as maintaining FLNC subcellular localization. Loss of FLNC-actin interaction in embryonic cardiomyocytes resulted in embryonic lethality and cardiac developmental defects, including ventricular wall malformation and reduced cardiomyocyte proliferation. Moreover, disruption of FLNC-actin interaction in adult cardiomyocytes led to severe dilated cardiomyopathy, enhanced lethality and dysregulation of key cytoskeleton components.
conclusionsOur data strongly support the crucial role of FLNC as a bridge between actin filaments and ECM through its interactions with actin, ITGB1, γ-SAG, and other associated proteins in cardiomyocytes. Disruption of FLN-actin interaction may result in detachment of actin filaments from the extracellular matrix, ultimately impairing normal cardiac development and function. These findings also provide insights into mechanisms underlying cardiomyopathy associated with genetic variants in FLNC ABD and other regions.
Indexed as
Identifiers
What OpenQuestion holds
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.