Hemidesmosomes are very small stud-like structures found in

keratinocyte Keratinocytes are the primary type of Cell (biology), cell found in the epidermis (skin), epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the stratum basale, basal layer (''str ...

s of the

epidermis The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water rele ...

of skin that attach to the

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...

. They are similar in form to

desmosome A desmosome (; "binding body"), also known as a macula adherens (plural: maculae adherentes) (Latin for ''adhering spot''), is a cell structure specialized for cell-to-cell adhesion. A type of junctional complex, they are localized spot-like adh ...

s when visualized by

electron microscopy An electron microscope is a microscope that uses a beam of accelerated electrons as a source of illumination. As the wavelength of an electron can be up to 100,000 times shorter than that of visible light photons, electron microscopes have a hi ...

, however, desmosomes attach to adjacent cells. Hemidesmosomes are also comparable to

focal adhesions In cell biology, focal adhesions (also cell–matrix adhesions or FAs) are large macromolecular assemblies through which mechanical force and regulatory signals are transmitted between the extracellular matrix (ECM) and an interacting cell. More p ...

, as they both attach cells to the extracellular matrix. Instead of

desmoglein The desmogleins are a family of desmosomal cadherins consisting of proteins DSG1, DSG2, DSG3, and DSG4. They play a role in the formation of desmosomes that join cells to one another. Pathology Desmogleins are targeted in the autoimmune disea ...

s and

desmocollin Desmocollins are a subfamily of desmosomal cadherins, the transmembrane constituents of desmosomes. They are co-expressed with desmogleins to link adjacent cells by extracellular adhesion. There are seven desmosomal cadherins in humans, three desmo ...

s in the extracellular space, hemidesmosomes utilize

integrin Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, ...

s. Hemidesmosomes are found in epithelial cells connecting the basal epithelial cells to the

lamina lucida The lamina lucida is a component of the basement membrane which is found between the epithelium and underlying connective tissue (e.g., epidermis and dermis of the skin). It is a roughly 40 nanometre wide electron-lucent zone between the plasma me ...

, which is part of the

basal lamina The basal lamina is a layer of extracellular matrix secreted by the epithelial cells, on which the epithelium sits. It is often incorrectly referred to as the basement membrane, though it does constitute a portion of the basement membrane. The ba ...

. Hemidesmosomes are also involved in signaling pathways, such as

migration or

carcinoma Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal ...

cell intrusion.

Structure

Hemidesmosomes can be categorized into two types based on their protein constituents. Type 1 hemidesmosomes are found in

stratified Stratification may refer to: Mathematics * Stratification (mathematics), any consistent assignment of numbers to predicate symbols * Data stratification in statistics Earth sciences * Stable and unstable stratification * Stratification, or st ...

and pseudo-stratified epithelium. Type 1 hemidesmosomes have five main elements:

α6 β4,

plectin Plectin is a giant protein found in nearly all mammalian cells which acts as a link between the three main components of the cytoskeleton: actin microfilaments, microtubules and intermediate filaments. In addition, plectin links the cytoskeleton ...

in its isoform 1a, i. e. P1a,

tetraspanin Tetraspanins are a family of membrane proteins found in all multicellular eukaryotes. Tetraspanins, also referred to as the transmembrane 4 superfamily (TM4SF) proteins, have four transmembrane alpha-helices and two extracellular domains, one s ...

protein

CD151 CD151 molecule (Raph blood group), also known as CD151 (Cluster of Differentiation 151), is a human gene. Function The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of ...

BPAG1 Dystonin (DST), also known as bullous pemphigoid antigen 1 (BPAG1), isoforms 1/2/3/4/5/8, is a protein that in humans is encoded by the ''DST'' gene. This gene encodes a member of the plakin protein family of adhesion junction plaque proteins. M ...

e, or bullous pemphigoid antigen isoform e, and BPAG2 (also known as BP180 or type 17 collagen). Type 1 hemidesmosomes are found in stratified and pseudostratified epithelial tissue. Type 2 hemidesmosomes contain integrin α6β4 and plectin without the BP antigens. Hemidesmosomes have two membrane-spanning components: Integrin α6β4 and Plectin 1a. Integrin α6β4 operates as a laminin-332 receptor. Integrin α6β4 is composed to two α and β subunit dimers. The larger β4 subunit has domains that bind to

fibronectin Fibronectin is a high- molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as collage ...

III and calcium. The α6 subunit binds to extracellular BP180, CD151 and laminin-322. When integrin α6β4 binds to Plectin 1a and BPAG1, it associates with the

keratin Keratin () is one of a family of structural fibrous proteins also known as ''scleroproteins''. Alpha-keratin (α-keratin) is a type of keratin found in vertebrates. It is the key structural material making up scales, hair, nails, feathers, ho ...

intermediate filament Intermediate filaments (IFs) are cytoskeletal structural components found in the cells of vertebrates, and many invertebrates. Homologues of the IF protein have been noted in an invertebrate, the cephalochordate ''Branchiostoma''. Intermedia ...

s in the cytoskeleton. Hemidesmosomes are linked to keratin by plectin isoform 1a from the

plakin A plakin is a protein that associates with junctional complexes and the cytoskeleton. Types include desmoplakin, envoplakin, periplakin, plectin, bullous pemphigoid antigen 1, corneodesmosin Corneodesmosin is a protein that in humans is encoded ...

protein family. Plectin is a 500 kDa protein with a long, rod-like domain and a domain at the end that contains an intermediate filament binding site. BPAG2, or (bullous pemphigoid antigen 2), is a transmembrane protein that exists adjacent to integrins, BPAG2 has domains that bind to plectin, integrin β4 subunit in the cytoplasm and integrin α6 and laminin-332 in the extracellular space. CD151, a protein of the

superfamily, resides on the cell surface of keratinocytes and vascular

endothelium The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...

. CD151 aids in hemidesmosome formation. BPAG1e is an

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

with multiple

isoforms A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...

that binds to integrin α6β4, BPAG2 and

keratin 5 Keratin 5, also known as KRT5, K5, or CK5, is a protein that is encoded in humans by the ''KRT5'' gene. It dimerizes with keratin 14 and forms the intermediate filaments (IF) that make up the cytoskeleton of basal epithelial cells. This protein i ...

and 14. The main role of BPAG1e is for hemidesmosome stability.

Diseases

Keeping the basal epidermal keratinocytes attached to the basal lamina is vital for skin

homeostasis In biology, homeostasis (British English, British also homoeostasis) Help:IPA/English, (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physics, physical, and chemistry, chemical conditions maintained by organism, living systems. Thi ...

. Genetic or acquired diseases that cause disruption of hemidesmosome components can lead to skin blistering disorders between different layers of the skin. These are collectively coined

epidermolysis bullosa Epidermolysis bullosa (EB) is a group of rare medical conditions that result in easy blistering of the skin and mucous membranes. Blisters occur with minor trauma or friction and are painful. Its severity can range from mild to fatal. Inherited E ...

, or EB. Typical symptoms include fragile skin, blister development, and erosion from minor physical stress. However, the disease also can manifest as erosions on the cornea, trachea, gastrointestinal tract, esophagus,

muscular dystrophy Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time. The disorders differ as to which muscles are primarily affe ...

and muscular deformity. Mutations in 12 different genes that code for parts of the hemidesmosome have led to epidermolysis bullosa. There are three types of EB: EB simplex (EBS), dystrophic EB (DEB) and junctional EB (JEB). In epidermolysis bullosa simplex, layers of the epidermis separate. EBS is caused by mutations coding for keratin, plectin and BPAG1e. With junctional epidermolysis bullosa, layers of the lamina lucida (part of the basal lamina) separate. This is caused by mutations in integrin α6β4, laminin 322 and BPAG2. In dystrophic epidermolysis bullosa, the layers of the

papillary dermis The dermis or corium is a layer of skin between the epidermis (with which it makes up the cutis) and subcutaneous tissues, that primarily consists of dense irregular connective tissue and cushions the body from stress and strain. It is divided in ...

separate from the

anchoring fibrils Anchoring fibrils (composed largely of type VII collagen) extend from the basal lamina of epithelial cells and attach to the lamina reticularis (also known as the reticular lamina) by wrapping around the reticular fiber ( collagen III) bundles. ...

. This is caused by mutations in the collagen 7 gene.

References

{{Authority control Cell anatomy Skin anatomy

Structure

Diseases

See also

References