ArticleBiochimica et biophysica acta2014
Valvular dystrophy associated filamin A mutations reveal a new role of its first repeats in small-GTPase regulation.
Article in Biochimica et biophysica acta, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- The Potential of Intertwining Gene Diagnostics and Surgery for Mitral Valve Prolapse.Journal of clinical medicine · 2023Review
- Genetic mechanisms underlying arrhythmogenic mitral valve prolapse: Current and future perspectives.Heart rhythm O2 · 2023Review
- Periostin/Filamin-A: A Candidate Central Regulatory Axis for Valve Fibrogenesis and Matrix Compaction.Frontiers in cell and developmental biology · 2021Article
- Desert hedgehog-primary cilia cross talk shapes mitral valve tissue by organizing smooth muscle actin.Developmental biology · 2020Article
- Article
- Critical Structural Defects Explain Filamin A Mutations Causing Mitral Valve Dysplasia.Biophysical journal · 2019Article
- Disrupted filamin A/αBlood · 2019Article
- Spatial Regulation of Valve Interstitial Cell Phenotypes within Three-Dimensional Micropatterned Hydrogels.ACS biomaterials science & engineering · 2019Article
- The effect of physiological stretch and the valvular endothelium on mitral valve proteomes.Experimental biology and medicine (Maywood, N.J.) · 2019Article
- Filamin-A as a Balance between Erk/Smad Activities During Cardiac Valve Development.Anatomical record (Hoboken, N.J. : 2007) · 2019Article
- Filamin A inhibits tumor progression through regulating BRCA1 expression in human breast cancer.Oncology letters · 2018Article
- Genetics of syndromic and non-syndromic mitral valve prolapse.Heart (British Cardiac Society) · 2018Review
- New insights into mitral valve dystrophy: a Filamin-A genotype-phenotype and outcome study.European heart journal · 2018Article
- Lung Transplantation for FLNA-Associated Progressive Lung Disease.The Journal of pediatrics · 2017Article
- Opposing FlnA and FlnB interactions regulate RhoA activation in guiding dynamic actin stress fiber formation and cell spreading.Human molecular genetics · 2017Article
- Mechanotransduction Mechanisms in Mitral Valve Physiology and Disease Pathogenesis.Frontiers in cardiovascular medicine · 2017Review
- Cyclic Mechanical Loading Is Essential for Rac1-Mediated Elongation and Remodeling of the Embryonic Mitral Valve.Current biology : CB · 2016Article
- Mitral valve disease--morphology and mechanisms.Nature reviews. Cardiology · 2015Review
- Cadherin-11 coordinates cellular migration and extracellular matrix remodeling during aortic valve maturation.Developmental biology · 2015Article
- MVP-Associated Filamin A Mutations Affect FlnA-PTPN12 (PTP-PEST) Interactions.Journal of cardiovascular development and disease · 2015Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Filamin A (FlnA) is a ubiquitous actin binding protein which anchors various transmembrane proteins to the cell cytoskeleton and provides a scaffold to many cytoplasmic signaling proteins involved in actin cytoskeleton remodeling in response to mechanical stress and cytokines stimulation. Although the vast majority of FlnA binding partners interact with the carboxy-terminal immunoglobulin like (Igl) repeats of FlnA, little is known on the role of the amino-N-terminal repeats. Here, using cardiac mitral valvular dystrophy associated FlnA-G288R and P637Q mutations located in the N-terminal Igl repeat 1 and 4 respectively as a model, we identified a new role of FlnA N-terminal repeats in small Rho-GTPases regulation. Using FlnA-deficient melanoma and HT1080 cell lines as expression systems we showed that FlnA mutations reduce cell spreading and migration capacities. Furthermore, we defined a signaling network in which FlnA mutations alter the balance between RhoA and Rac1 GTPases activities in favor of RhoA and provided evidences for a role of the Rac1 specific GTPase activating protein FilGAP in this process. Together our work ascribed a new role to the N-terminal repeats of FlnA in Small GTPases regulation and supports a conceptual framework for the role of FlnA mutations in cardiac valve diseases centered around signaling molecules regulating cellular actin cytoskeleton in response to mechanical stress.
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