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{{short description|Structures connecting keratinocyte cells to the extracellular matrix}}
{{Infobox anatomy
| Name = Hemidesmosome
| Latin = hemidesmosoma
| Image = Ultrastructure of tracheal hemidesmosomes in mice.JPEG
| Caption = 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 [[Laminin, gamma 2|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.<ref name="pmid16483354">{{cite journal |vauthors=Nguyen NM, Pulkkinen L, Schlueter JA, Meneguzzi G, Uitto J, Senior RM |title=Lung development in laminin γ2 deficiency: abnormal tracheal hemidesmosomes with normal branching morphogenesis and epithelial differentiation |journal=[[Respir. Res.]] |volume=7 |issue=1 |pages=28 |year=2006 |pmid=16483354 |pmc=1386662 |doi=10.1186/1465-9921-7-28 |doi-access=free }}</ref>
| Image2 =
| Caption2 =
| Precursor =
| System =
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'''Hemidesmosomes''' are very small stud-like structures found in [[keratinocyte]]s of the [[Epidermis (skin)|epidermis]] of skin that attach to the [[extracellular matrix]]. They are similar in form to [[desmosome]]s when visualized by [[electron microscopy]]; however, desmosomes attach to adjacent cells. Hemidesmosomes are also comparable to [[focal adhesion]]s, as they both attach cells to the extracellular matrix. Instead of [[desmoglein]]s and [[desmocollin]]s in the extracellular space, hemidesmosomes utilize [[integrin]]s. Hemidesmosomes are found in epithelial cells connecting the basal epithelial cells to the [[lamina lucida]], which is part of the [[basal lamina]].<ref name=":0">{{Cite journal|last1=Walko|first1=Gernot|last2=Castañón|first2=Maria J.|last3=Wiche|first3=Gerhard|date=May 2015|title=Molecular architecture and function of the hemidesmosome|journal=Cell and Tissue Research|volume=360|issue=2|pages=363–378|doi=10.1007/s00441-014-2061-z|issn=1432-0878|pmc=4544487|pmid=25487405}}</ref> Hemidesmosomes are also involved in signaling pathways, such as keratinocyte migration or [[carcinoma]] cell intrusion.<ref>{{Cite journal|last1=Wilhelmsen|first1=Kevin|last2=Litjens|first2=Sandy H. M.|last3=Sonnenberg|first3=Arnoud|date=April 2006|title=Multiple functions of the integrin alpha6beta4 in epidermal homeostasis and tumorigenesis|journal=Molecular and Cellular Biology|volume=26|issue=8|pages=2877–2886|doi=10.1128/MCB.26.8.2877-2886.2006|issn=0270-7306|pmc=1446957|pmid=16581764}}</ref>

== Structure ==
Hemidesmosomes can be categorized into two types based on their protein constituents. Type 1 hemidesmosomes are found in [[stratified squamous epithelium|stratified]] and [[Pseudostratified epithelium|pseudo-stratified epithelium]]. Type 1 hemidesmosomes have five main elements: [[integrin]] [[Integrin alpha 6|α6]][[Integrin beta 4|β4]], [[plectin]] in its isoform 1a, i. e. P1a, [[tetraspanin]] protein [[CD151]], [[BPAG1]]e, or bullous pemphigoid antigen isoform e, and [[BPAG2]] (also known as BP180 or type 17 collagen).<ref name=":0" /> Type 1 hemidesmosomes are found in stratified and pseudostratified epithelial tissue. Type 2 hemidesmosomes contain integrin α6β4 and plectin without the BP antigens.<ref>{{Cite journal|last1=Fontao|first1=L.|last2=Stutzmann|first2=J.|last3=Gendry|first3=P.|last4=Launay|first4=J. F.|date=1999-08-01|title=Regulation of the type II hemidesmosomal plaque assembly in intestinal epithelial cells|journal=Experimental Cell Research|volume=250|issue=2|pages=298–312|doi=10.1006/excr.1999.4549|issn=0014-4827|pmid=10413585}}</ref>

Hemidesmosomes have two membrane-spanning components: Integrin α6β4 and BPAG2. Integrin α6β4 operates as a [[Laminin|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 filament]]s in the cytoskeleton.<ref name=":0" />

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 [[Keratin 14|14]]. The main role of BPAG1e is for hemidesmosome stability.<ref name=":0" />

== 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.<ref name=":0" /> However, the disease also can manifest as erosions on the cornea, trachea, gastrointestinal tract, esophagus, [[muscular dystrophy]] and muscular deformity.<ref>{{Cite journal|last1=Bardhan|first1=Ajoy|last2=Bruckner-Tuderman|first2=Leena|last3=Chapple|first3=Iain L. C.|last4=Fine|first4=Jo-David|last5=Harper|first5=Natasha|last6=Has|first6=Cristina|last7=Magin|first7=Thomas M.|last8=Marinkovich|first8=M. Peter|last9=Marshall|first9=John F.|last10=McGrath|first10=John A.|last11=Mellerio|first11=Jemima E.|date=2020-09-24|title=Epidermolysis bullosa|url=https://www.nature.com/articles/s41572-020-0210-0|journal=Nature Reviews Disease Primers|language=en|volume=6|issue=1|page=78|doi=10.1038/s41572-020-0210-0|pmid=32973163|s2cid=221861310|issn=2056-676X|url-access=subscription}}</ref>

Mutations in 12 different genes that code for parts of the hemidesmosome have led to epidermolysis bullosa.<ref>{{Cite journal|last1=Fine|first1=Jo-David|last2=Bruckner-Tuderman|first2=Leena|last3=Eady|first3=Robin A. J.|last4=Bauer|first4=Eugene A.|last5=Bauer|first5=Johann W.|last6=Has|first6=Cristina|last7=Heagerty|first7=Adrian|last8=Hintner|first8=Helmut|last9=Hovnanian|first9=Alain|date=June 2014|title=Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification|journal=Journal of the American Academy of Dermatology|volume=70|issue=6|pages=1103–1126|doi=10.1016/j.jaad.2014.01.903|issn=1097-6787|pmid=24690439|doi-access=free}}</ref> There are three types of EB: [[Epidermolysis bullosa simplex|EB simplex]] (EBS), [[Dystrophic Epidermolysis Bullosa|dystrophic EB]] (DEB) and [[Junctional epidermolysis bullosa (medicine)|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, type VII, alpha 1|collagen 7]] gene.

==See also==
* [[Desmosome]]
* [[Epidermolysis bullosa]]
* [[Focal adhesion]]

==References==
{{Reflist|2}}

{{Commons category|Hemidesmosomes|lcfirst=yes}}

{{CellJunction}}
{{Authority control}}

[[Category:Cell anatomy]]
[[Category:Skin anatomy]]

Hemidesmosome - Revision history

imported>OAbot: Open access bot: url-access updated in citation with #oabot.