ArticlePLoS genetics2011
Targeted proteolysis of plectin isoform 1a accounts for hemidesmosome dysfunction in mice mimicking the dominant skin blistering disease EBS-Ogna.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 65 citations in OpenAlex.
- Mechanics of cell sheets: plectin as an integrator of cytoskeletal networks.Open biology · 2025Review
- Role of plectin and its interacting molecules in cancer.Medical oncology (Northwood, London, England) · 2023Review
- Mutation update: The spectra of PLEC sequence variants and related plectinopathies.Human mutation · 2022Article
- Plectin-mediated cytoskeletal crosstalk controls cell tension and cohesion in epithelial sheets.The Journal of cell biology · 2022Article
- Keratins as an Inflammation Trigger Point in Epidermolysis Bullosa Simplex.International journal of molecular sciences · 2021Review
- Plectin in Skin Fragility Disorders.Cells · 2021Review
- Review
- Review
- Plectin ensures intestinal epithelial integrity and protects colon against colitis.Mucosal immunology · 2021Article
- Review
- Complexes of α6β4 integrin and vimentin act as signaling hubs to regulate epithelial cell migration.Journal of cell science · 2018Article
- An Arf6- and caveolae-dependent pathway links hemidesmosome remodeling and mechanoresponse.Molecular biology of the cell · 2018Article
- No major role for rare plectin variants in arrhythmogenic right ventricular cardiomyopathy.PloS one · 2018Article
- Advances in understanding the molecular basis of skin fragility.F1000Research · 2018Review
- The rod domain is not essential for the function of plectin in maintaining tissue integrity.Molecular biology of the cell · 2015Article
- Molecular architecture and function of the hemidesmosome.Cell and tissue research · 2015Review
- UV exposure modulates hemidesmosome plasticity, contributing to long-term pigmentation in human skin.The Journal of pathology · 2015Article
- Molecular architecture and function of the hemidesmosome.Cell and tissue research · 2015Review
- Structural insights into Ca2+-calmodulin regulation of Plectin 1a-integrin β4 interaction in hemidesmosomes.Structure (London, England : 1993) · 2015Article
- Interaction of plectin with keratins 5 and 14: dependence on several plectin domains and keratin quaternary structure.The Journal of investigative dermatology · 2014Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Autosomal recessive mutations in the cytolinker protein plectin account for the multisystem disorders epidermolysis bullosa simplex (EBS) associated with muscular dystrophy (EBS-MD), pyloric atresia (EBS-PA), and congenital myasthenia (EBS-CMS). In contrast, a dominant missense mutation leads to the disease EBS-Ogna, manifesting exclusively as skin fragility. We have exploited this trait to study the molecular basis of hemidesmosome failure in EBS-Ogna and to reveal the contribution of plectin to hemidesmosome homeostasis. We generated EBS-Ogna knock-in mice mimicking the human phenotype and show that blistering reflects insufficient protein levels of the hemidesmosome-associated plectin isoform 1a. We found that plectin 1a, in contrast to plectin 1c, the major isoform expressed in epidermal keratinocytes, is proteolytically degraded, supporting the notion that degradation of hemidesmosome-anchored plectin is spatially controlled. Using recombinant proteins, we show that the mutation renders plectin's 190-nm-long coiled-coil rod domain more vulnerable to cleavage by calpains and other proteases activated in the epidermis but not in skeletal muscle. Accordingly, treatment of cultured EBS-Ogna keratinocytes as well as of EBS-Ogna mouse skin with calpain inhibitors resulted in increased plectin 1a protein expression levels. Moreover, we report that plectin's rod domain forms dimeric structures that can further associate laterally into remarkably stable (paracrystalline) polymers. We propose focal self-association of plectin molecules as a novel mechanism contributing to hemidesmosome homeostasis and stabilization.
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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.