ArticleMolecular biology of the cell2004
Epidermolysis bullosa simplex-type mutations alter the dynamics of the keratin cytoskeleton and reveal a contribution of actin to the transport of keratin subunits.
Article in Molecular biology of the cell, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 99 citations in OpenAlex.
- Keratins coordinate tissue spreading by balancing spreading forces with tissue material properties.Nature communications · 2026Article
- Mechanics of cell sheets: plectin as an integrator of cytoskeletal networks.Open biology · 2025Review
- Rupture strength of living cell monolayers.Nature materials · 2024Article
- Molecular determinants of intrinsic cellular stiffness in health and disease.Biophysical reviews · 2022Review
- A CaCells · 2022Article
- Impact of N-Terminal Tags on De Novo Vimentin Intermediate Filament Assembly.International journal of molecular sciences · 2022Article
- Detrimental Effects of IFN-γ on an Epidermolysis Bullosa Simplex Cell Model and Protection by a Humanized Anti-IFN-γ Monoclonal Antibody.JID innovations : skin science from molecules to population health · 2022Article
- Plectin-mediated cytoskeletal crosstalk controls cell tension and cohesion in epithelial sheets.The Journal of cell biology · 2022Article
- Cell and Tissue Nanomechanics: From Early Development to Carcinogenesis.Biomedicines · 2022Review
- Keratins as an Inflammation Trigger Point in Epidermolysis Bullosa Simplex.International journal of molecular sciences · 2021Review
- A cell-based drug discovery assay identifies inhibition of cell stress responses as a new approach to treatment of epidermolysis bullosa simplex.Journal of cell science · 2021Article
- Article
- Growth, lifetime, directional movement and myosin-dependent motility of mutant keratin granules in cultured cells.Scientific reports · 2021Article
- Article
- Keratin Dynamics and Spatial Distribution in Wild-Type and K14 R125P Mutant Cells-A Computational Model.International journal of molecular sciences · 2020Article
- Cortical stiffness of keratinocytes measured by lateral indentation with optical tweezers.PloS one · 2020Article
- Induction of Transgene Suppression in Plants via External Application of Synthetic dsRNA.International journal of molecular sciences · 2019Article
- An ex vivo RNA trans-splicing strategy to correct human generalized severe epidermolysis bullosa simplex.The British journal of dermatology · 2019Article
- Types I and II Keratin Intermediate Filaments.Cold Spring Harbor perspectives in biology · 2018Review
- Cut and Paste: Efficient Homology-Directed Repair of a Dominant Negative KRT14 Mutation via CRISPR/Cas9 Nickases.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dominant keratin mutations cause epidermolysis bullosa simplex by transforming keratin (K) filaments into aggregates. As a first step toward understanding the properties of mutant keratins in vivo, we stably transfected epithelial cells with an enhanced yellow fluorescent protein-tagged K14R125C mutant. K14R125C became localized as aggregates in the cell periphery and incorporated into perinuclear keratin filaments. Unexpectedly, keratin aggregates were in dynamic equilibrium with soluble subunits at a half-life time of <15 min, whereas filaments were extremely static. Therefore, this dominant-negative mutation acts by altering cytoskeletal dynamics and solubility. Unlike previously postulated, the dominance of mutations is limited and strictly depends on the ratio of mutant to wild-type protein. In support, K14R125C-specific RNA interference experiments resulted in a rapid disintegration of aggregates and restored normal filaments. Most importantly, live cell inhibitor studies revealed that the granules are transported from the cell periphery inwards in an actin-, but not microtubule-based manner. The peripheral granule zone may define a region in which keratin precursors are incorporated into existing filaments. Collectively, our data have uncovered the transient nature of keratin aggregates in cells and offer a rationale for the treatment of epidermolysis bullosa simplex by using short interfering RNAs.
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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.