Hemidesmosome

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Hemidesmosome
Ultrastructure of tracheal hemidesmosomes in mice.JPEG
Ultrastructure of tracheal hemidesmosomes in mice. In a normal mouse (a) there are well-defined, organized hemidesmosomes with darkened areas in the lamina densa abutting the hemidesmosome (arrows). In contrast, hemidesmosomes in Lamc2 -/- tracheas (b) are less organized, the intracellular component is more diffuse, and the lamina densa directly below the hemidesmosomal areas lacks the electron density seen in the littermate control (arrows). From Nguyen et al., 2006. [1]
Details
Identifiers
Latin hemidesmosoma
MeSH D022002
TH H1.00.01.1.02029
FMA 67415
Anatomical terminology

Hemidesmosomes are very small stud-like structures found in keratinocytes of the epidermis of skin that attach to the extracellular matrix. They are similar in form to desmosomes when visualized by electron microscopy, however, desmosomes attach to adjacent cells. Hemidesmosomes are also comparable to focal adhesions, as they both attach cells to the extracellular matrix. Instead of desmogleins and desmocollins in the extracellular space, hemidesmosomes utilize integrins. Hemidesmosomes are found in epithelial cells connecting the basal epithelial cells to the lamina lucida, which is part of the basal lamina. [2] Hemidesmosomes are also involved in signaling pathways, such as keratinocyte migration or carcinoma cell intrusion. [3]

Contents

Structure

Hemidesmosomes can be categorized into two types based on their protein constituents. Type 1 hemidesmosomes are found in stratified and pseudo-stratified epithelium. Type 1 hemidesmosomes have five main elements: integrin α6 β4, plectin in its isoform 1a, i. e. P1a, tetraspanin protein CD151, BPAG1e, or bullous pemphigoid antigen isoform e, and BPAG2 (also known as BP180 or type 17 collagen). [2] Type 1 hemidesmosomes are found in stratified and pseudostratified epithelial tissue. Type 2 hemidesmosomes contain integrin α6β4 and plectin without the BP antigens. [4]

Hemidesmosomes have two membrane-spanning components: Integrin α6β4 and BPAG2. 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 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 intermediate filaments in the cytoskeleton. [2]

Hemidesmosomes are linked to keratin by plectin isoform 1a from the plakin 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 tetraspanin superfamily, resides on the cell surface of keratinocytes and vascular endothelium. CD151 aids in hemidesmosome formation. BPAG1e is an antigen with multiple isoforms that binds to integrin α6β4, BPAG2 and keratin 5 and 14. The main role of BPAG1e is for hemidesmosome stability. [2]

Diseases

Keeping the basal epidermal keratinocytes attached to the basal lamina is vital for skin homeostasis. 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, or EB. Typical symptoms include fragile skin, blister development, and erosion from minor physical stress. [2] However, the disease also can manifest as erosions on the cornea, trachea, gastrointestinal tract, esophagus, muscular dystrophy and muscular deformity. [5]

Mutations in 12 different genes that code for parts of the hemidesmosome have led to epidermolysis bullosa. [6] 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 separate from the anchoring fibrils. This is caused by mutations in the collagen 7 gene.

See also

Related Research Articles

<span class="mw-page-title-main">Intermediate filament</span> Cytoskeletal structure

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.

<span class="mw-page-title-main">Cell adhesion</span> Process of cell attachment

Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indirect interaction, where cells attach to surrounding extracellular matrix, a gel-like structure containing molecules released by cells into spaces between them. Cells adhesion occurs from the interactions between cell-adhesion molecules (CAMs), transmembrane proteins located on the cell surface. Cell adhesion links cells in different ways and can be involved in signal transduction for cells to detect and respond to changes in the surroundings. Other cellular processes regulated by cell adhesion include cell migration and tissue development in multicellular organisms. Alterations in cell adhesion can disrupt important cellular processes and lead to a variety of diseases, including cancer and arthritis. Cell adhesion is also essential for infectious organisms, such as bacteria or viruses, to cause diseases.

<span class="mw-page-title-main">Desmosome</span> Cell junction involved in cell-to-cell adhesion

A desmosome, also known as a macula adherens, is a cell structure specialized for cell-to-cell adhesion. A type of junctional complex, they are localized spot-like adhesions randomly arranged on the lateral sides of plasma membranes. Desmosomes are one of the stronger cell-to-cell adhesion types and are found in tissue that experience intense mechanical stress, such as cardiac muscle tissue, bladder tissue, gastrointestinal mucosa, and epithelia.

<span class="mw-page-title-main">Epidermolysis bullosa</span> Rare medical conditions that result in easy blistering of the skin and mucous membranes

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 EB is a rare disease with a prevalence in the United States of 8.2 per million live births. Those with mild cases may not develop symptoms until they start to crawl or walk. Complications may include esophageal narrowing, squamous cell skin cancer, and the need for amputations.

<span class="mw-page-title-main">Keratin 14</span> Protein-coding gene in the species Homo sapiens

Keratin 14 is a member of the type I keratin family of intermediate filament proteins. Keratin 14 was the first type I keratin sequence determined. Keratin 14 is also known as cytokeratin-14 (CK-14) or keratin-14 (KRT14). In humans it is encoded by the KRT14 gene.

<span class="mw-page-title-main">Basement membrane</span> Thin fibrous layer between the cells and the adjacent connective tissue in animals

The basement membrane, also known as base membrane is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between epithelial tissues including mesothelium and endothelium, and the underlying connective tissue.

<span class="mw-page-title-main">Laminin</span> Protein in the extracellular matrix

Laminins are a family of glycoproteins of the extracellular matrix of all animals. They are major constituents of the basement membrane, namely the basal lamina. Laminins are vital to biological activity, influencing cell differentiation, migration, and adhesion.

<span class="mw-page-title-main">Plectin</span> Mammalian protein found in Homo sapiens

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 to junctions found in the plasma membrane that structurally connect different cells. By holding these different networks together, plectin plays an important role in maintaining the mechanical integrity and viscoelastic properties of tissues.

<span class="mw-page-title-main">Epidermolysis bullosa simplex</span> Medical condition

Epidermolysis bullosa simplex (EBS) is a disorder resulting from mutations in the genes encoding keratin 5 or keratin 14.

<span class="mw-page-title-main">Keratin 5</span>

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 is involved in several diseases including epidermolysis bullosa simplex and breast and lung cancers.

<span class="mw-page-title-main">Collagen, type XVII, alpha 1</span> Mammalian protein found in humans

Collagen XVII, previously called BP180, is a transmembrane protein which plays a critical role in maintaining the linkage between the intracellular and the extracellular structural elements involved in epidermal adhesion, identified by Diaz and colleagues in 1990.

<span class="mw-page-title-main">CD151</span> Protein-coding gene in the species Homo sapiens

CD151 molecule, also known as CD151, is a human gene.

<span class="mw-page-title-main">Integrin beta 4</span> Protein-coding gene in the species Homo sapiens

Integrin, beta 4 (ITGB4) also known as CD104, is a human gene.

<span class="mw-page-title-main">Laminin subunit gamma-2</span> Protein-coding gene in the species Homo sapiens

Laminin subunit gamma-2 is a protein that in humans is encoded by the LAMC2 gene.

<span class="mw-page-title-main">Dystonin</span> Neurologically significant human protein

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.

<span class="mw-page-title-main">Laminin, alpha 3</span> Protein-coding gene in the species Homo sapiens

Laminin subunit alpha-3 is a protein that in humans is encoded by the LAMA3 gene.

<span class="mw-page-title-main">Laminin, beta 3</span> Protein-coding gene in the species Homo sapiens

Laminin subunit beta-3 is a protein that in humans is encoded by the LAMB3 gene.

Anchoring fibrils extend from the basal lamina of epithelial cells and attach to the lamina reticularis by wrapping around the reticular fiber bundles. The basal lamina and lamina reticularis together make up the basement membrane. Anchoring fibrils are essential to the functional integrity of the dermoepidermal junction.

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 desmocollins and four desmogleins. Desmosomal cadherins allow desmosomes to contribute to the integrity of tissue structure in multicellular living organisms.

Junctional epidermolysis bullosa is a skin condition characterized by blister formation within the lamina lucida of the basement membrane zone.

References

  1. ↑ Nguyen NM, Pulkkinen L, Schlueter JA, Meneguzzi G, Uitto J, Senior RM (2006). "Lung development in laminin γ2 deficiency: abnormal tracheal hemidesmosomes with normal branching morphogenesis and epithelial differentiation". Respir. Res. 7 (1): 28. doi: 10.1186/1465-9921-7-28 . PMC   1386662 . PMID   16483354.
  2. 1 2 3 4 5 Walko, Gernot; Castañón, Maria J.; Wiche, Gerhard (May 2015). "Molecular architecture and function of the hemidesmosome". Cell and Tissue Research. 360 (2): 363–378. doi:10.1007/s00441-014-2061-z. ISSN   1432-0878. PMC   4544487 . PMID   25487405.
  3. ↑ Wilhelmsen, Kevin; Litjens, Sandy H. M.; Sonnenberg, Arnoud (April 2006). "Multiple functions of the integrin alpha6beta4 in epidermal homeostasis and tumorigenesis". Molecular and Cellular Biology. 26 (8): 2877–2886. doi:10.1128/MCB.26.8.2877-2886.2006. ISSN   0270-7306. PMC   1446957 . PMID   16581764.
  4. ↑ Fontao, L.; Stutzmann, J.; Gendry, P.; Launay, J. F. (1999-08-01). "Regulation of the type II hemidesmosomal plaque assembly in intestinal epithelial cells". Experimental Cell Research. 250 (2): 298–312. doi:10.1006/excr.1999.4549. ISSN   0014-4827. PMID   10413585.
  5. ↑ Bardhan, Ajoy; Bruckner-Tuderman, Leena; Chapple, Iain L. C.; Fine, Jo-David; Harper, Natasha; Has, Cristina; Magin, Thomas M.; Marinkovich, M. Peter; Marshall, John F.; McGrath, John A.; Mellerio, Jemima E. (2020-09-24). "Epidermolysis bullosa". Nature Reviews Disease Primers. 6 (1): 78. doi:10.1038/s41572-020-0210-0. ISSN   2056-676X. PMID   32973163. S2CID   221861310.
  6. ↑ Fine, Jo-David; Bruckner-Tuderman, Leena; Eady, Robin A. J.; Bauer, Eugene A.; Bauer, Johann W.; Has, Cristina; Heagerty, Adrian; Hintner, Helmut; Hovnanian, Alain (June 2014). "Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification". Journal of the American Academy of Dermatology. 70 (6): 1103–1126. doi: 10.1016/j.jaad.2014.01.903 . ISSN   1097-6787. PMID   24690439.
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