Desmosomes: Adhesion Answers to Skin

Mar 1, 2011 | Contact Author | By: Katie Schaefer, Cosmetics & Toiletries magazine
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Title: Desmosomes: Adhesion Answers to Skin
dermosomesx cell adhesionx wound healingx
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Keywords: dermosomes | cell adhesion | wound healing

Abstract: Garrod became interested in cell adhesion after reading a paper on the differential adhesion hypothesis by Malcolm Steinberg, and he more recently discovered the mechanism that allows these structures to tightly bind cells together.

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K Anderson, Dermosomes: Adhesion Answers to Skin, Cosm & Toil 126(3) 232 (2011)

Desmosomes, junctions that bind cells of epithelial tissues together, were first isolated in 1974 by Christine J. Skerrow and A. Gedeon Matoltsy, whose work led to studies of desmosomes in cell adhesion by future scientists,1 such as David Garrod, PhD, a professor in the faculty of life sciences at the University of Manchester, United Kingdom. While desmosomes are present in all epithelial tissues, they are more predominant in tissues subject to mechanical stress, such as epidermal and cardiac tissues. Garrod became interested in cell adhesion after reading a paper on the differential adhesion hypothesis by Malcolm Steinberg, and he more recently discovered the mechanism that allows these structures to tightly bind cells together.

Tightly Bound

Desmosomes are membrane domains with clearly defined structures. According to Garrod, “They have a dense cytoplasmic structure, [the plaque], that links to the intermediate filament cytoskeleton of cells. The desmosomal adhesion molecules have tails [c termini] in the plaque and across the membrane of the cell.” Garrod explained that the gluelike molecules in desmosomes binding cells together are called desmosomal cadherins and according to Garrod, there are two main types: desmogleins and desmocollins, of which there are more specific subtypes.

To identify and further study the binding of desmosomal adhesion molecules, Garrod’s team employed a homobiofunctional cross-linker with reactive groups at both ends to link between lysine residues in proteins that are close in proximity. Identifying the connection between adhesion molecules was made possible with knowledge of their molecular weights. “We knew the molecular weight of each [dermosomal adhesion] molecule, so if two were bound together, the molecular weight would be doubled, which is precisely what we found,” Garrod said.

“In humans there are four types of desmogleins and three types of desmocollins, all of which appear in the skin,” Garrod said. The novel discovery, however, was that of the two types each of desmogleins and desmocollins expressed by the human keratinocytes studied by Garrod, each only bound to its same type. Further, subtypes of desmogleins and desmocollins only bound to molecules of their same subtype. Garrod proposes this creates better adhesion. “We hypothesize that the method of linking has something to do with the strength of adhesion,” he said, noting the team is still trying to understand this mechanism.

Cell Binding Applications

Understanding the binding mechanisms in desmosomes could lead to the treatment of skin and heart diseases resulting from their defects, says Garrod. Pemphigus vulgaris, for example, is a rare autoimmune disease in which one of the desmosomal adhesion molecules is targeted by an auto-antibody that causes loss of cell adhesion in the epidermis and oral mucosa. Garrod believes that elucidating the role of the desmosomal adhesion molecules in P. vulgaris may lead to its treatment, since some of the molecules in this disease are present on the surface of skin cells—outside of the desmosomes. “These molecules are not tightly bound to other molecules in the way we believe they are bound in desmosomes,” he said, suggesting this “extradesmosomal molecule” is the primary target of the auto-antibody that causes the epidermal cells to lose adhesion.

Although the team is interested in treating skin and heart diseases, its primary focus is on wound healing. “We are looking at ways to modify the adhesiveness of desmosomes ... to change the strength at which they bind together in order to promote wound healing,” he said, noting its potential to treat non-healing wounds in diabetics or elderly individuals. Garrod has evidence that these wounds may not heal due to desmosomes being locked in a tightly adhesive manner. He explained, “The epidermis is a thin layer but is tough because desmosomes lock the cells together. When the epidermis is wounded, the cells have to free up to migrate and close the wound, then lock themselves up again to cover the wound.” Current studies in wound healing are under way and new findings are expected this spring.

In principle, Garrod believes he can modify desmosomal adhesion by activating the enzyme protein kinase C. He noted that while there are compounds that activate the enzyme, they are unrefined and have side effects. “If we can understand how these molecules are bound together, it may be possible to modulate them from the outside [rather than reacting with the signaling mechanism inside].” Garrod further hypothesizes that the mechanism behind desmosome binding operates in any disease-causing lesions in the skin and pending funding, he plans to study psoriasis and P. vulgaris in an attempt to benefit these skin diseases.

1. CJ Skerrow and AG Matoltsy, Isolation of epidermal desmosomes, J Cell Biol Nov 1, 63 (2) 515–523 (1974)



Biography for David Garrod, PhD

David Garrod, PhD

David Garrod, PhD, has been a professor of developmental biology at the University of Manchester, United Kingdom, since 1989. Before joining the university, he was a lecturer, senior lecturer and a reader in medical oncology for the University of Southampton. Garrod has written for a number of scientific publications, and his current research focuses on cell adhesion, signalling, differentiation and development of epithelial cells.

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