Identifying Plectin Isoform Functions through Animal Models
| Autor: | Castañón, Maria J., Wiche, Gerhard |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
plectin
QH301-705.5 Review macromolecular substances Biology conditional gene targeting Epidermolysis bullosa simplex Genetic model medicine Animals Humans Protein Isoforms mouse models epidermolysis bullosa Biology (General) Muscular dystrophy Intermediate filament vascular permeability Zebrafish sarcolemma myofibrillar myopathies Hemidesmosome simple epithelia Skeletal muscle General Medicine Plectin medicine.disease biology.organism_classification Cell biology Disease Models Animal hemidesmosomes medicine.anatomical_structure Muscular Dystrophies Limb-Girdle Epidermolysis Bullosa Simplex Mutation neuromuscular synapse |
| Zdroj: | Cells Cells, Vol 10, Iss 2453, p 2453 (2021) |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells10092453 |
| Popis: | Plectin, a high-molecular-weight cytoskeletal linker protein, binds with high affinity to intermediate filaments of all types and connects them to junctional complexes, organelles, and inner membrane systems. In addition, it interacts with actomyosin structures and microtubules. As a multifunctional protein, plectin has been implicated in several multisystemic diseases, the most common of which is epidermolysis bullosa simplex with muscular dystrophy (EBS-MD). A great part of our knowledge about plectin’s functional diversity has been gained through the analysis of a unique collection of transgenic mice that includes a full (null) knockout (KO), several tissue-restricted and isoform-specific KOs, three double KOs, and two knock-in lines. The key molecular features and pathological phenotypes of these mice will be discussed in this review. In summary, the analysis of the different genetic models indicated that a functional plectin is required for the proper function of striated and simple epithelia, cardiac and skeletal muscle, the neuromuscular junction, and the vascular endothelium, recapitulating the symptoms of humans carrying plectin mutations. The plectin-null line showed severe skin and muscle phenotypes reflecting the importance of plectin for hemidesmosome and sarcomere integrity; whereas the ablation of individual isoforms caused a specific phenotype in myofibers, basal keratinocytes, or neurons. Tissue-restricted ablation of plectin rendered the targeted cells less resilient to mechanical stress. Studies based on animal models other than the mouse, such as zebrafish and C. elegans, will be discussed as well. |
| Databáze: | OpenAIRE |
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