ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2011
The calcium ATPase SERCA2 regulates desmoplakin dynamics and intercellular adhesive strength through modulation of PKCα signaling.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 76 citations in OpenAlex.
- Darier disease-A review highlighting new insights from the Darier Disease International Task Force.Journal of the European Academy of Dermatology and Venereology : JEADV · 2026Review
- Failed metabolic adaptation to stress contributes to epidermal cell adhesion defects in Darier disease.Science advances · 2026Article
- Cadherin regulation of endoplasmic reticulum-plasma membrane contact sites.Cell reports · 2026Article
- Pemphigus Vulgaris Autoantibodies Induce an Endoplasmic Reticulum Stress Response.The Journal of investigative dermatology · 2025Article
- Pumping the Breaks on Acantholytic Skin Disorders: Targeting Calcium Pumps, Desmosomes, and Downstream Signaling in Darier, Hailey-Hailey, and Grover Disease.The Journal of investigative dermatology · 2025Review
- Patients with Darier disease have an increased risk of keratinocyte carcinoma: a Swedish registry-based nationwide cohort study.Orphanet journal of rare diseases · 2024Article
- Grover's Disease Association with Cutaneous Keratinocyte Cancers: More than a Coincidence?International journal of molecular sciences · 2024Review
- Dantrolene corrects cellular disease features of Darier disease and may be a novel treatment.EMBO molecular medicine · 2024Article
- The Distinctive Role of Gluconic Acid in Retarding Percutaneous Drug Permeation: Formulation of Lidocaine-Loaded Chitosan Nanoparticles.Pharmaceutics · 2024Article
- Targeting SERCA2 in organotypic epidermis reveals MEK inhibition as a therapeutic strategy for Darier disease.JCI insight · 2023Article
- Transcriptional profiling of rare acantholytic disorders suggests common mechanisms of pathogenesis.JCI insight · 2023Article
- Endoplasmic reticulum tethering by desmosomes.Nature cell biology · 2023Article
- Architecture and dynamics of a desmosome-endoplasmic reticulum complex.Nature cell biology · 2023Article
- Pitfalls in the Application of Dispase-Based Keratinocyte Dissociation Assay for In Vitro Analysis of Pemphigus Vulgaris.Vaccines · 2022Article
- A Case of Darier's Disease with a Novel Missense Mutation inClinical, cosmetic and investigational dermatology · 2022Article
- RNA-seq reveals tight junction-relevant erythropoietic fate induced by OCT4 in human hair follicle mesenchymal stem cells.Stem cell research & therapy · 2020Article
- Article
- Enhancement of Cardiac Store Operated Calcium Entry (SOCE) within Novel Intercalated Disk Microdomains in Arrhythmic Disease.Scientific reports · 2019Article
- RPGRIP1L is required for stabilizing epidermal keratinocyte adhesion through regulating desmoglein endocytosis.PLoS genetics · 2019Article
- Autoantibody Signaling in Pemphigus Vulgaris: Development of an Integrated Model.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Darier's disease (DD) is an inherited autosomal-dominant skin disorder characterized histologically by loss of adhesion between keratinocytes. DD is typically caused by mutations in sarcoendoplasmic reticulum Ca(2+)-ATPase isoform 2 (SERCA2), a major regulator of intracellular Ca(2+) homeostasis in the skin. However, a defined role for SERCA2 in regulating intercellular adhesion remains poorly understood. We found that diminution of SERCA2 function by pharmacological inhibition or siRNA silencing in multiple human epidermal-derived cell lines was sufficient to disrupt desmosome assembly and weaken intercellular adhesive strength. Specifically, SERCA2-deficient cells exhibited up to a 60% reduction in border translocation of desmoplakin (DP), the desmosomal cytolinker protein necessary for intermediate filament (IF) anchorage to sites of robust cell-cell adhesion. In addition, loss of SERCA2 impaired the membrane translocation of protein kinase C α (PKCα), a known regulator of DP-IF association and desmosome assembly, to the plasma membrane by up to 70%. Exogenous activation of PKCα in SERCA2-deficient cells was sufficient to rescue the defective DP localization, desmosome assembly, and intercellular adhesive strength to levels comparable to controls. Our findings indicate that SERCA2-deficiency is sufficient to impede desmosome assembly and weaken intercellular adhesive strength via a PKCα-dependent mechanism, implicating SERCA2 as a novel regulator of PKCα signaling.
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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.