Desmoglein-2: A Novel Regulator of Apoptosis in the Intestinal Epithelium

• Authors: Porfirio Nava, Emory University; Mike G. Laukoetter, Emory University; Ann M. Hopkins, University College Dublin; Oskar Laur, Emory University; Kirsten Gerner-Smidt, Emory University; Kathleen J. Green, Northwestern University; Charles Parkos, Emory University; Asma Nusrat, Emory University
• Journal Title: Molecular Biology of the Cell
• Volume: Volume 18, Number 11
• Publisher: American Society for Cell Biology | 2007-11, Pages 4565-4578
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1091/mbc.E07-05-0426
• Subjects: Biology, Cell; Biology, Molecular; Health Sciences, Pathology

Abstract

Intestinal epithelial intercellular junctions regulate barrier properties, and they have been linked to epithelial differentiation and programmed cell death (apoptosis). However, mechanisms regulating these processes are poorly defined. Desmosomes are critical elements of intercellular junctions; they are punctate structures made up of transmembrane desmosomal cadherins termed desmoglein-2 (Dsg2) and desmocollin-2 (Dsc2) that affiliate with the underlying intermediate filaments via linker proteins to provide mechanical strength to epithelia. In the present study, we generated an antibody, AH12.2, that recognizes Dsg2. We show that Dsg2 but not another desmosomal cadherin, Dsc2, is cleaved by cysteine proteases during the onset of intestinal epithelial cell (IEC) apoptosis. Small interfering RNA-mediated down-regulation of Dsg2 protected epithelial cells from apoptosis. Moreover, we report that a C-terminal fragment of Dsg2 regulates apoptosis and Dsg2 protein levels. Our studies highlight a novel mechanism by which Dsg2 regulates IEC apoptosis driven by cysteine proteases during physiological differentiation and inflammation.