INTRODUCTION Hemidesmosomes are multiprotein complexes that mediate adhesion of epithelial cells to the underlying basement membrane in stratified and certain complex epithelia

Hemidesmosomes are multiprotein complexes that mediate adhesion of epithelial cells to the underlying basement membrane in stratified and certain complex epithelia (for reviews see Borradori and Sonnenberg, 1999; Nievers et al., 1999). They are composed of several transmembrane and cytoplasmic proteins that connect the keratin intermediate filament (IF) system to the extracellular matrix (ECM). Tissue fragility and blistering disorders arise from abnormalities in hemidesmosomal components or their associated structures, i.e. IFs and the extracellular matrix, demonstrating the importance of hemidesmosomes in maintaining dermoepidermal adhesion and integrity (Stanley, 1995; Christiano and Uitto, 1996). The α6β4 integrin and the bullous pemphigoid antigen 180 (BP180) are the two known transmembrane components of the hemidesmosome (Stepp et al., 1990; Jones et al., 1991; Sonnenberg et al., 1991; Giudice et al., 1992; Hopkinson et al., 1992; Li et al., 1993), both of which are thought to bind laminin-5 (Niessen et al., 1994b; Reddy et al., 1998), a major component of the epidermal basement membrane. The cytoplasmic components of hemidesmosomes include the bullous pemphigoid antigen 230 (BP230) and HD1/plectin. Both belong to the plakin family, which comprises proteins that act as molecular bridges between different cytoskeletal networks and/or between the cytoskeleton and cell adhesion structures (Fuchs and Yang, 1999). BP230 as well as HD1/plectin contain an IF binding site, involved in connecting the hemidesmosome to the keratin IF system. In addition to the 963 Journal of Cell Science 113, 963-973 (2000) Printed in Great Britain © The Company of Biologists Limited 2000 JCS1214