PUBLICATION
Identifying Plectin Isoform Functions through Animal Models
- Authors
- Castañón, M.J., Wiche, G.
- ID
- ZDB-PUB-210929-4
- Date
- 2021
- Source
- Cells 10(9): (Review)
- Registered Authors
- Keywords
- conditional gene targeting, epidermolysis bullosa, hemidesmosomes, mouse models, myofibrillar myopathies, neuromuscular synapse, plectin, sarcolemma, simple epithelia, vascular permeability
- MeSH Terms
-
- Humans
- Mutation*
- Disease Models, Animal*
- Animals
- Epidermolysis Bullosa Simplex/etiology
- Epidermolysis Bullosa Simplex/metabolism
- Epidermolysis Bullosa Simplex/pathology*
- Protein Isoforms
- Muscular Dystrophies, Limb-Girdle/etiology
- Muscular Dystrophies, Limb-Girdle/metabolism
- Muscular Dystrophies, Limb-Girdle/pathology*
- Plectin/genetics
- Plectin/metabolism*
- PubMed
- 34572100 Full text @ Cells
Citation
Castañón, M.J., Wiche, G. (2021) Identifying Plectin Isoform Functions through Animal Models. Cells. 10(9):.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping