Desmoglein-2: a novel regulator of apoptosis in the intestinal epithelium.
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.
Nava
Porfirio
P
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.
Laukoetter
Mike G
MG
Hopkins
Ann M
AM
Laur
Oskar
O
Gerner-Smidt
Kirsten
K
Green
Kathleen J
KJ
Parkos
Charles A
CA
Nusrat
Asma
A
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens / Q000276:immunology; D017209:Apoptosis; D002460:Cell Line; D003106:Colon / Q000166:cytology* / Q000378:metabolism*; D051301:Desmoglein 2 / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015536:Down-Regulation; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism; D008969:Molecular Sequence Data; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation; D051185:gamma Catenin / Q000378:metabolism