Schematic of the basement membrane zone and intercellular desmosomal adhesion

Intermediate filaments composed of keratin 5 and 14 insert on the keratin (cytoskeletal) linker proteins plectin and BPAG1 (BP230) at the superior aspect of the basement membrane zone. Plectin and BPAG1 interact with transmembrane alpha-6 beta-4 integrin and type XVII collagen (BP180/BPAG2), forming hemidesmosomes that attach basal keratinocytes to the underlying basement membrane. Anchoring filaments jut out below the hemidesmosome and include laminin-332 and laminin-311, which associate with type XVII collagen and alpha-6 beta-4 integrin, and also laminin-511, type IV collagen, and nidogen, thereby forming the lamina densa. Anchoring fibrils extend perpendicularly as banded projections from the lamina densa and contain polymeric associations of type VII collagen molecules that intertwine between dermal interstitial collagen fibrils. Type VII collagen triple helices attach the lamina densa to the papillary dermis and are critical for the integrity of the epidermal-dermal junction through their ability to bind laminin-332. Intercellular junction is mediated by desmosomes, whose intracellular protein components include desmoplakin (interacting with intermediate filament network), plakophilin, and plakoglobin, the last 2 of which connect to the transmembrane cadherin tails (composed of desmoglein, desmocollin). Focal adhesions are multiprotein cell membrane assemblies that link the cellular cytoskeleton to the surrounding extracellular matrix. Fermitin family homolog 1 (kindlin-1) is a focal adhesion component and serves as an intracellular adapter protein that associates the actin cytoskeleton to focal adhesions. Mutations in the gene FERMT1 (KIND1) cause KEB.