Plakin Proteins, Hemidesmosomes and Human Disease

Abstract

The plakin proteins are a family of cytolinker proteins that connect elements of the cell cytoskeleton to each other and to junctional complexes at the cell membrane. There are seven mammalian plakin proteins and they are characterised by the presence of a plakin domain and/or a plakin repeat domain. The plakins play a vital role in maintaining the integrity of tissues, such as the skin and heart, which are subjected to mechanical stress. Two plakin proteins, plectin and bullous pemphigoid antigen 1 (BPAG1), are essential components of hemidesmosomes, cell–extracellular matrix junctions of epithelial cells, and inherited mutations in either can result in the skin blistering disease epidermolysis bullosa simplex. Mutations in the desmosomal plakin protein desmoplakin can cause the heart muscle disorder arrhythmogenic right ventricular dysplasia, a common cause of sudden cardiac arrest and death in young adults. Plakin proteins are targeted by pathogenic autoantibodies in the skin blistering diseases bullous pemphigoid and paraneoplastic pemphigus. Key Concepts: The plakin proteins are a family of cytolinker proteins that connect elements of the cell cytoskeleton to each other and to junctional complexes at the cell membrane. Seven plakin proteins are found in mammals; plectin, BPAG1, desmoplakin, envoplakin, periplakin, microtubule–actin crosslinking factor 1 and epiplakin. Plectin and BPAG1 are important constituents of hemidesmosomes, cell–extracellular matrix junctions. Mutations in plakin proteins can result in skin blistering disease, muscular dystrophy, autonomic neuropathy and cardiomyopathy. Plakin proteins have been implicated in the autoimmune skin blistering diseases bullous pemphigoid and paraneoplastic pemphigus.

Cell-Matrix Interactions Contribute to Barrier Function in Human Colon Organoids

“…While these laminin chains did not demonstrate an increase in response to Aquamin® in colon organoids, several other hemidesmosomal proteins were detected, and a subset of these (dystonin, plectin, desmoplakin, and epiplakin) were also increased by Aquamin® as compared to control ( Figure 1 ). The plakins are critical linkers between laminin in the hemidesmosomes and intermediate filaments ( 40 , 41 ). Similarly, additional hemidesmosomal components (BP180 or Collagen Type XVII α1 Chain, and CD151) were also detected in both datasets.…”

Cell-matrix adhesion contributes to permeability control in human colon organoids

“…While these laminin chains did not demonstrate an increase in response to Aquamin ® in colon organoids, several other hemidesmosomal proteins were detected, and a subset of these (plectin, desmoplakin and epiplakin) were increased by Aquamin ® as compared to control. The plakins are critical linkers between laminin in the hemidesmosomes and intermediate filaments (38,39).…”