Part of the glue that holds humans together also plays a role in the way skin cells differentiate, according to new research from the lab of Kathleen Green, PhD, Joseph L. Mayberry Sr. Professor of Pathology and Toxicology.
Published in the Journal of Clinical Investigation, investigators looked at one of the adhesion molecules that help form the outer layer of the skin, which regulates water loss while also acting as the body's major barrier against environmental elements.
“There are a surprisingly large number of molecules that help form this barrier and they are distributed in a highly-patterned manner, prompting investigators to hypothesize that they do more than just mediate cell-cell adhesion,” said Green, professor of pathology and dermatology. “For many years, the molecule we studied – desmoglein 1 – has been considered to primarily play a structural role in holding epidermal cells together, however, this research uncovered that it also acts to promote the skin’s differentiation program.”
Led by postdoctoral fellow Robert Harmon, PhD ’13, the Green lab examined the association desmoglein 1 has with a specific structural protein – Erbin. By identifying the interaction of the two proteins, which together dampen a signaling pathway that leads to differentiation, the group revealed the previously unknown role desmoglein 1 plays in skin development.
“I think that all of us involved in the project are excited about the final outcome and its broader implications for skin biology and possibly cancer,” Green said.
One question that flows directly from the findings is whether the protein interaction plays a role in tumor suppression. It has been noted by other researchers that the loss of desmoglein 1 is linked with poor prognosis in cancers of the head and neck.
“We are working on revealing even more of desmoglein’s secrets,” Green said. “In addition to its role in regulating signaling, it also governs the shape of cells as they journey to the tissue surface. Oksana Nekrasova, a postdoctoral fellow in my lab, is already exploring another binding partner that emerged from our work.”
The project was funded by R01 grants from the National Institutes of Arthritis, Musculoskeletal, and Skin Disease (NIAMS) and the National Cancer Institute. The NIAMS-funded Northwestern University Skin Disease Research Center also provided critical support.