Hemidesmosomes

Hemidesmosomes are multiprotein adhesion complexes located at the basal surface of epithelial cells, where they mediate adhesion to the underlying basement membrane. They anchor the keratin intermediate filament cytoskeleton inside the cell to components of the basal lamina, enabling stable attachment and resistance to mechanical stress.

The core transmembrane components include integrin α6β4 and the transmembrane collagen XVII (BP180). Extracellularly, these proteins interact with laminin-332 (laminin-5) in the basement membrane. Intracellularly, a dense plaque formed by plectin and BP230 (BPAG1) connects to keratin filaments, strengthening the linkage.

The organization and mechanism of hemidesmosomes create a robust, end-to-end connection between the cell interior and the extracellular matrix. The extracellular region links to basement membrane proteins, while the intracellular plaque anchors to the keratin network, enabling the cell to resist shear and stretching forces in tissues such as skin and mucosa.

Functionally, hemidesmosomes contribute to tissue integrity in stratified and glandular epithelia and participate in signaling through integrin pathways. They are dynamically remodeled during development, wound healing, and disease.

Clinical relevance includes autoimmune and genetic disorders affecting adhesion. Autoantibodies against BP180 or BP230 can cause bullous pemphigoid, a blistering autoimmune disease. Genetic mutations in hemidesmosomal components—such as ITGA6, ITGB4, COL17A1, and subunits of laminin-332 (LAMA3, LAMB3, LAMC2)—underlie forms of epidermolysis bullosa and other basement membrane defects, leading to epidermal detachment under mechanical stress.