Plakophilins

Protein group that belongs to the so-called armadillo proteins. Plakophilins are proteins that function as cell adhesion molecules. In addition to their structural functions, they also assume functions in signalling pathways. Proteins with such dual functions are able to mediate changes in morphology and gene expression during tissue and organ development. Thus they fundamentally influence cell shape and mobility.

Plakophilins belong to the so-called armadillo proteins. "Armadillo" refers to a characteristic, repetitive sequence of amino acids (Armadillo repeat). This was first discovered in Drosophila (fruit fly). Armadillo proteins include plakophilins, beta-catenin, alpha-importin and others.

In desmosomes, plakophilins regulate the organization of the plaques and the anchoring of keratin filaments. Plakophilins are expressed cell type-specific.

Plakophilin 1 was first described as a keratin-binding protein and stabilizes desmosomal proteins and keratins at the plasma membrane.

Plakophilins 2 and 3 show a broader expression pattern and are also expressed in simple epithelia. Thus, plakophilin 2 is also found in the cell contacts of the shiny stripes in cardiac muscle cells. Mutations in the plakophilin 2 gene lead to familial cardiomyopathy. Plakophilin 2 is overexpressed in various cardiomyopathies. tumors such as gliomas (Zhang et al. 2017).

Mutations in the PKP1 gene, which codes for plakophilin 1, cause the "Ectodermal dysplasia/skin fragility syndrome" in humans, a skin disease with traumatically induced blistering, reduced intercellular adhesion, palmoplantar keratosis and woolly hair. The number, size and stability of desmosomes are reduced and keratin anchorage is disturbed. In addition, keratin aggregates are formed in the cytoplasm.

1. Kashyap S et al (2015) Ectodermal Dysplasia-Skin Fragility Syndrome: A Rare Case Report. Indian J Dermatol 60:421.
2. Klauke B et al. (2017) High proportion of genetic cases in patients with advanced cardiomyopathyincluding
   a novel homozygous plakophilin 2 gene mutation. PLoS One 12:e0189489.
3. Rietscher K et al (2018) 14-3-3 proteins regulate desmosomal adhesion via plakophilin. J Cell Sci 131 pii: jcs212191.