Title

Desmosomes and desmosomal cadherin function in skin and heart diseases-advancements in basic and clinical research.

Document Type

Article

Publication Date

1-1-2010

Comments

This article has been peer reviewed. It was published in: Dermatology Research and Practice.

2010: 725647.

The published version is available at DOI: 10.1155/2010/725647. Copyright © Hindawi.

Abstract

In the last two decades desmosomal research has developed from a highly specialized area of cell biology to an area of biomedical research aimed at elucidating the role of these cell junctions in tissue and organ development and homeostasis.

Until the late 1980s, desmosomal research focused, to a large extent, on the morphological characterization of desmosomes and the biochemical identification of desmosomal proteins. Towards the end of that decade, the first desmosomal transmembrane proteins (desmogleins and desmocollins) were cloned, demonstrating that these proteins are sequence related to cadherins, a family of calcium-dependent cell adhesion proteins. Subsequent knockout experiments in mice, published in the 1990s, demonstrated that at least some of the desmosomal cadherins (e.g., desmoglein 3) are required to maintain tissue integrity in the oral mucosa (see the paper of Ganeshan et al.). Around the same time, it was shown that patients who suffer from autoimmune diseases characterized by skin and mucous membrane blistering produce autoantibodies against desmogleins 1 and 3 (DSG1, DSG3). These two observations suggested that the loss of normal desmosome function could lead to tissue fragility disorders.

Subsequent to the identification of pemphigus as a desmosomal disease, reports began to emerge suggesting that mutations in desmosomal genes can cause a variety of skin blistering disorders and cardiomyopathy (see the paper by J. Li and G. L. Radice).

Recently the question has emerged: Are all desmosomal diseases caused by a loss of cell adhesion? Mounting evidence suggests that abnormal cell signaling might contribute to the pathophysiology of at least certain types of desmosomal diseases, such as pemphigus (see the paper of M. Bektas et al. and D. Brennan et al.). The putative contributions of cell adhesion defects and abnormal cell signaling in diseases like pemphigus are still under intense debate. We can expect to see a continued influx of exciting new findings in this area.

The present special issue is a collection of reviews and original research articles that focus on fundamental aspects of desmosome biology and on clinical research relating to desmosomal diseases of the skin, mucous membranes, and heart. These papers are also examples of how a synergistic approach that utilizes the tools of genetic engineering in mice, human genetics, cell and molecular biology and immunology have led to a significant advancement of our understanding of the pathological mechanisms underlying desmosomal diseases. We sincerely thank the authors for their high-quality and exciting contributions. We hope that these provocative papers will stimulate discussions and promote future collaborations.