Desmoglein-2: A novel regulator of apoptosis in the intestinal epithelium

Porfirio Nava, Mike G. Laukoetter, Ann M. Hopkins, Oskar Laur, Kirsten Gerner-Smidt, Kathleen J. Green, Charles A. Parkos, Asma Nusrat*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4565-4578
Number of pages14
JournalMolecular biology of the cell
Volume18
Issue number11
DOIs
StatePublished - Nov 2007

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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