Plectin

Plectin belongs to the protein family of plakins. Plectin is found in eukaryotes, including humans. Plectin is a 500 kDa structural protein that binds to intermediate filaments and is detectable in the cytoplasm of almost all cells, especially in muscle and cardiac muscle cells, in epidermal cells, nerve cells and in cells of the placenta. Plectin cross-links actin, tubulin and some other intermediate filaments.

In the epidermis, basal epithelial cells are connected to the underlying basal lamina by hemidesmosomes. The intracellular proteins BP230 and plectin provide the connection. BP230 binds plectin via BP180 and integrin alpha 6 beta 4 which in turn binds to laminin 5 and ultimately makes contact with collagen type VII. Thus, pectin functions as an important anchor protein of the inner hemidesmosomal plaque. Thus, pectin is significant for epidermal integrity and cross-linking with other structural proteins.

Hemidesmosomes are adhesion complexes of multiple proteins that connect epithelial cells to the basal matrix.

In humans, plectin is encoded by the plectin gene (PLEC, PLEC1), which is located on chromosome 8 (8q24.3). Mutations in PLEC cause several rare diseases that are grouped under the term plectinopathies. The most common disease is autosomal recessive inherited epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), which is characterized by blistering of the skin and progressive muscle weakness (Winter L et al. 2016).

Mutations in the PLEC gene can lead to different phenotypes of epidermolysis bullosa simplex(epidermolysis bullosa simplex with muscular dystrophy, epidermolysis bullosa simplex with pyloric atresia, and epidermolysis bullosa simplex type Ogna) as well as a late-onset autosomal recessive limb-girdling form of muscular dystrophy (LGMD2Q).

In anti-plectin pemphigoid, a blistering autoimmune disease, antibodies are produced against hemidesomal plectin.

1. Castañón MJ et al. (2013) Plectin-intermediate filament partnership in skin, skeletal muscle, and peripheral nerve. In: Histochemistry and cell biology 140: 33-53.
2. Chan LS (1997) Human skin basement membrane in health and in autoimmune diseases. Front Biosci 2:d343-52.
3. Georgi M et al (2001) Autoantigens of subepidermal bullous autoimmune dermatoses. Dermatologist 52:1079-1089.
4. Selma Osmanagic-Myers S et al (2006) Plectin-controlled keratin cytoarchitecture affects MAP kinases involved in cellular stress response and migration. J Cell Biol 174: 557-568.
5. Winter L et al (2016) Downstream effects of plectin mutations in epidermolysis bullosa simplex with muscular dystrophy. Acta Neuropathol Commun 4: 44.
6. Zrelski MM et al (2021) Muscle-related plectinopathies. Cells10:2480.