Molecular architecture and function of the hemidesmosome

Abstract

Hemidesmosomes are multiprotein complexes that facilitate the stable adhesion of basal epithelial cells to the underlying basement membrane. The mechanical stability of hemidesmosomes relies on multiple interactions of a few protein components that form a membrane-embedded tightly-ordered complex. The core of this complex is provided by integrin α6β4 and P1a, an isoform of the cytoskeletal linker protein plectin that is specifically associated with hemidesmosomes. Integrin α6β4 binds to the extracellular matrix protein laminin-332, whereas P1a forms a bridge to the cytoplasmic keratin intermediate filament network. Other important components are BPAG1e, the epithelial isoform of bullous pemphigoid antigen 1, BPAG2, a collagen-type transmembrane protein and CD151. Inherited or acquired diseases in which essential components of the hemidesmosome are missing or structurally altered result in tissue fragility and blistering. Modulation of hemidesmosome function is of crucial importance for a variety of biological processes, such as terminal differentiation of basal keratinocytes and keratinocyte migration during wound healing and carcinoma invasion. Here, we review the molecular characteristics of the proteins that make up the hemidesmosome core structure and summarize the current knowledge about how their assembly and turnover are regulated by transcriptional and post-translational mechanisms.

Functional Morphology of the Arm Spine Joint and Adjacent Structures of the Brittlestar Ophiocomina nigra (Echinodermata: Ophiuroidea)

“…The support cells of the epidermis are connected to the lamina densa at structural complexes whose morphology is identical to that of mammalian hemidesmosomes, in that they include components corresponding to mammalian anchoring filaments, sub-basal dense plate (both components located within the lamina lucida) and cytoplasmic plaque linking the plasma membrane to intracellular tonofibrils [55]. Those hemidesmosomes closest to, and on either side of, the flexion plane at the deepest level of the constrictions were much larger than those located at more superficial levels, which presumably is an adaptation for resisting the greater shear and tensile forces occurring between the support cells and basement membrane near the flexion plane when the epidermis is stretched and compressed by spine movements.…”

The Role of Collagen XVII in Cancer: Squamous Cell Carcinoma and Beyond

“…Collagen XVII is a 180-kD type II transmembrane protein and structural component of the dermoepidermal anchoring complex, which facilitates adhesion of keratinocytes and certain other epithelial cells to the underlying basement membrane (10). Its gene, COL17A1, has been mapped to chromosome 10q24.3 (15,16). Collagen XVII along with integrin α6β4, CD151, plectin, and BP230 are components of type I hemidesmosomes (HDs), which are responsible for cell-stromal adherence, cell polarization, and spatial organization of tissue architecture (10,16).…”

Blood Vessel Epicardial Substance (BVES) in junctional signaling and cancer

“…Hemides mosomes couple the basal membrane of the epithelium to the underlying basal lamina and coordinate with the more laterally localized desmosomes to help nucleate intermediate filament networks of the cytoskeleton. 5 Gap junctions connect neighboring cells and allow for direct cell-cell passage of ions, metabolites, and second messengers through hexamers consisting mainly of connexin proteins. 6 Adherens junctions initiate and maintain cell-cell contacts by coupling the transmembrane glycoprotein E-cadherin and cytoplasmic constituents p120-catenin, β-catenin, and α-catenin with the actin cytoskeleton.…”