Inferior Portion of Basal KeratinocyteHemidesmosome (HD)- Appears as thickened area interspersed along plasma membrane of basal keratinocyte; provides attachment between basal keratinocyte and extracellular matrix
- Composed of following macromolecules: BPAG1, BPAG2, integrin, and plectin
- Tonofilaments (or keratin filaments) insert into hemidesmosomes
BPAG1 (230 kDa)- Intracellular glycoprotein in plakin family which is associated with the cytoplasmic plaque domain of hemidesmosome; promotes adhesion of intermediate filaments with plasma membrane (likely binds or anchors filaments to HD)
BPAG2 (180 kDa, Collagen XVII)- Transmembrane (mainly extracellular) protein belonging to collagen family; interacts with BPAG1, β4 integrin, and plectin
- Divisions of protein: amino terminus (intracellular), transmembrane portion, extracellular carboxy terminus (in lamina lucida); most antibodies in bullous disorders target extracellular domain (proximal NC16A and distal carboxy terminus)
- NC16A domain (first extracellular segment): typically targeted in bullous pemphigoid (BP), pemphigoid gestationis, linear IgA bullous dermatosis (LABD)
- Carboxy terminus (C-terminal): targeted in cicatricial pemphigoid (CP)
| | | | | | Three target antigens seen in CP: BPAG2, laminin-5 (epiligrin), α 6 β 4 integrin | | | | | |
Integrin- Transmembrane cell receptor consisting of two subunits (α and β); located at basal layer of epidermis and promotes both cell-cell and cell-matrix interactions
- α 6 β 4: hemidesmosome-associated integrin; binds intermediate filaments intracellularly, laminin-5 (now called laminin-332) in lamina lucida, and HD proteins (plectin, BPAG2)
| | | | | | Autoantibody to β 4 → CP (ocular); b 4 mutation → JEB with pyloric atresia | | | | | |
Plectin- Intracellular protein belonging to plakin family; associated with cytoplasmic plaque domain of hemidesmosome; links intermediate filaments to plasma membrane and cross-links HD proteins
| | | | | | Plectin mutation → EBS w/ muscular dystrophy | | | | | |
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