Desmocollin

Desmocollins are a subfamily of desmosomal cadherins, the transmembrane constituents of desmosomes.[3][4] 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.[4] Desmosomal cadherins allow desmosomes to contribute to the integrity of tissue structure in multicellular living organisms.[5]

Crystal structure of human Desmocollin-1 ectodomain, PDB 5IRY[1][2]

Structure

Three isoforms of desmocollin proteins have been identified.[6]

Each desmocollin gene encodes a pair of proteins: a longer 'a' form and a shorter 'b' form. The 'a' and 'b' forms differ in the length of their C-terminus tails. The protein pair is generated by alternative splicing.[4]

Desmocollin has four cadherin-like extracellular domains, an extracellular anchor domain, and an intracellular anchor domain. Additionally, the 'a' form has an intracellular cadherin-like sequence domain, which provides binding sites for other desmosomal proteins such as plakoglobin.[4]

Expression

The desmosomal cadherins are expressed in tissue-specific patterns. Desmocollin-2 and desmoglein-2 are found in all desmosome-containing tissues such as colon and cardiac muscle tissues, while other desmosomal cadherins are restricted to stratified epithelial tissues.[4]

All seven desmosomal cadherins are expressed in epidermis, but in a differentiation-specific manner. The '2' and '3' isoforms of desmocollin and desmoglein are expressed in the lower epidermal layers, and the '1' proteins and desmoglein-4 are expressed in the upper epidermal layers. Different isoforms are located in the same individual cells, and single desmosomes contain more than one isoform of both desmocollin and desmoglein.[4]

It is unclear why there are multiple desmosomal cadherin isoforms. It is thought that they may have different adhesive properties that are required at different levels in stratified epithelia or that they have specific functions in epithelial differentiation.[4]

Disorders

Desmosomes are involved in cell-cell adhesion, and are particularly important for the integrity of heart and skin tissue. Because of this, desmocollin gene mutations can affect the adhesion of cells that undergo mechanical stress, notably cardiomyocytes and keratinocytes. Genetic disorders associated with desmocollin gene mutations include Carvajal syndrome, striate palmoplantar keratoderma, Naxos disease, and arrhythmogenic right ventricular cardiomyopathy.[7]

There is also evidence that autoimmunity against desmosomal cadherins contributes to cardiac inflammation associated with arrhythmogenic right ventricular cardiomyopathy, and that anti-desmosomal cadherin antibodies may represent new therapeutic targets.[8]

See also

References
  1. Harrison, Oliver J.; Brasch, Julia; Lasso, Gorka; Katsamba, Phinikoula S.; Ahlsen, Goran; Honig, Barry; Shapiro, Lawrence (2016-06-28). "Structural basis of adhesive binding by desmocollins and desmogleins". Proceedings of the National Academy of Sciences. 113 (26): 7160–7165. doi:10.1073/pnas.1606272113. ISSN 0027-8424. PMC 4932976. PMID 27298358.
  2. Bank, RCSB Protein Data. "RCSB PDB - 5IRY: Crystal structure of human Desmocollin-1 ectodomain". www.rcsb.org. Retrieved 2020-04-25.
  3. Desmocollins at the US National Library of Medicine Medical Subject Headings (MeSH)
  4. Garrod D, Chidgey M (March 2008). "Desmosome structure, composition and function". Biochimica et Biophysica Acta (BBA) - Biomembranes. Apical Junctional Complexes Part I. 1778 (3): 572–87. doi:10.1016/j.bbamem.2007.07.014. PMID 17854763.
  5. Sun C, Wang L, Yang XX, Jiang YH, Guo XL (June 2019). "The aberrant expression or disruption of desmocollin2 in human diseases". International Journal of Biological Macromolecules. 131: 378–386. doi:10.1016/j.ijbiomac.2019.03.041. PMID 30851326.
  6. Delva E, Tucker DK, Kowalczyk AP (August 2009). "The desmosome". Cold Spring Harbor Perspectives in Biology. 1 (2): a002543. doi:10.1101/cshperspect.a002543. PMC 2742091. PMID 20066089.
  7. Brodehl A, Stanasiuk C, Anselmetti D, Gummert J, Milting H (May 2019). "Incorporation of desmocollin-2 into the plasma membrane requires N-glycosylation at multiple sites". FEBS Open Bio. 9 (5): 996–1007. doi:10.1002/2211-5463.12631. PMC 6487837. PMID 30942563.
  8. Chatterjee, Diptendu; Fatah, Meena; Akdis, Deniz; Spears, Danna A; Koopmann, Tamara T; Mittal, Kirti; Rafiq, Muhammad A; Cattanach, Bruce M; Zhao, Qili; Healey, Jeff S; Ackerman, Michael J (2018-11-21). "An autoantibody identifies arrhythmogenic right ventricular cardiomyopathy and participates in its pathogenesis". European Heart Journal. 39 (44): 3932–3944. doi:10.1093/eurheartj/ehy567. ISSN 0195-668X. PMC 6247665. PMID 30239670.
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