IN SIGHT
with David Garrod, PhD
Desmosomes: Adhesion Answers in Skin
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.
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.
References
1. CJ Skerrow and AG Matoltsy, Isolation of epidermal desmosomes, J Cell Biol Nov 1, 63 (2)
515–523 (1974)
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.
232 | Cosmetics & Toiletries® magazine www.CosmeticsandToiletries.com
Vol. 126, No. 3/March 2011
