Plectin Deficiency in Fibroblasts Deranges Intermediate Filament and Organelle Morphology, Migration, and Adhesion

Zrelski MM, Hösele S, Kustermann M, Fichtinger P, Kah DTE, Athanasiou I, Esser PR, Wagner A, Herzog R, Kratochwill K, Goldmann WH, Kiritsi D, Winter L (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Journal of Investigative Dermatology Elsevier

Book Volume: 144

Pages Range: 547-562.e9

Journal Issue: 3

DOI: 10.1016/j.jid.2023.08.020

Abstract

Plectin, a highly versatile and multifunctional cytolinker, has been implicated in several multisystemic disorders. Most sequence variations in the human plectin gene (PLEC) cause epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), an autosomal recessive skin-blistering disorder associated with progressive muscle weakness. In this study, we performed a comprehensive cell biological analysis of dermal fibroblasts from three different patients with EBS-MD, where PLEC expression analyses revealed preserved mRNA levels in all cases, whereas full-length plectin protein content was significantly reduced or completely absent. Downstream effects of pathogenic PLEC sequence alterations included massive bundling of vimentin intermediate filament networks, including the occurrence of ring-like nuclei-encasing filament bundles, elongated mitochondrial networks, and abnormal nuclear morphologies. We found that essential fibroblast functions such as wound healing, migration, or orientation upon cyclic stretch were significantly impaired in the cells of patients with EBS-MD. Finally, EBS-MD fibroblasts displayed reduced adhesion capacities, which could be attributed to smaller focal adhesion contacts. Our study not only emphasizes plectin's functional role in human skin fibroblasts, it also provides further insights into the understanding of EBS-MD–associated disease mechanisms.

Authors with CRIS profile

Delf-Thorge Eric Kah Lehrstuhl für Biophysik

Involved external institutions

Medizinische Universität Wien AT Austria (AT) Universitätsklinikum Freiburg DE Germany (DE)

How to cite

APA:

Zrelski, M.M., Hösele, S., Kustermann, M., Fichtinger, P., Kah, D.-T.E., Athanasiou, I.,... Winter, L. (2024). Plectin Deficiency in Fibroblasts Deranges Intermediate Filament and Organelle Morphology, Migration, and Adhesion. Journal of Investigative Dermatology, 144(3), 547-562.e9. https://dx.doi.org/10.1016/j.jid.2023.08.020

MLA:

Zrelski, Michaela M., et al. "Plectin Deficiency in Fibroblasts Deranges Intermediate Filament and Organelle Morphology, Migration, and Adhesion." Journal of Investigative Dermatology 144.3 (2024): 547-562.e9.

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