Plakins are large proteins with binding domains for microtubules, microfilaments, intermediate filaments, and membrane-associated protein complexes at cell junctions. Plakin functions are evolutionarily conserved and are primarily involved in organizing the different components of the cytoskeleton by crosslinking them to each other and connecting them to the cell-matrix and cell adhesion complexes. They are also known to interact with signal transducers, serve as scaffolds for signaling complexes and modulate vesicle trafficking.
Plakins were initially found associated with intermediate filaments in desmosomes and hemidesmosomes, which are cell junctions in the epithelial tissues. Therefore, their function was believed to be restricted to maintaining epithelial tissue integrity. However, recent research has resulted in the discovery of new plakins with unique isoforms that arise through the alternative splicing of the plakin gene locus. These isoforms show tissue-specific expression profiles and have unique domain organizations and functions. These isoforms can also associate with the other cytoskeletal filaments and are functional in non-epithelial cells. For example, research on mice and invertebrates has demonstrated the role of plakins in non-epidermal cells such as neurons.
Disorders associated with Plakins
Plakins are cytolinkers crucial to cellular development and maintenance of tissue integrity. Therefore, any defect in the gene coding for plakin can result in various diseases that affect the skin, neuronal tissue, and cardiac and skeletal muscle. Mammals have seven proteins belonging to the plakins, such as desmoplakin, envoplakin, epiplakin, bullous pemphigoid antigen 1, microtubule‐actin crosslinking factor 1, periplakin, and plectin. In humans, mutations in any of these plakin genes result in disorders of the skin and muscular system. For example, mutations in genes coding for plectin result in a disease called epidermolysis bullosa simplex with muscular dystrophy, which results in fragile skin easily prone to blistering and damage and weakening of muscles over time.
