The schemes depict major molecular components of HDs (left) and desmosomes (right)
HDs are integrin-mediated structures that are specialized in epithelial cell attachment to the ECM by providing a link between the extracellular basement membrane and the mechanical stress-bearing intracellular KF network. In epidermis, type I HDs can be found, which consist of transmembraneous α6β4-integrin dimers and BPAG2 (type XVII collagen, COL17A1) that are respectively anchored to K5/K14 IFs via cytolinker plectin 1a and BPAG1e. Desmosomes consist of transmembrane proteins, desmogleins and desmocollins, whose extracellular domains interconnect to form cell–cell adhesion, and their cytoplasmic tails bind to plakoglobin and plakophilins, which are also known as armadillo proteins. These armadillo proteins are then bound to desmoplakin, a cytoskeleton-associated protein, which finally anchors cytoplasmic KFs to desmosomes.