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Desmocollin 2 regulates proliferation in the intestinal epithelial cell line SK‐CO15 through activation of the small GTPase Rap1
Author(s) -
Kolegraff Keli,
Nava Porfirio,
Severson Eric,
Koch Stefan,
Laukoetter Mike,
Parkos Charles,
Nusrat Asma
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.464.4
Subject(s) - microbiology and biotechnology , rap1 , cell growth , gene knockdown , cytokeratin , cadherin , focal adhesion , small gtpase , biology , chemistry , cell , cell culture , signal transduction , immunology , immunohistochemistry , biochemistry , genetics
Desmosomes (DMs) are essential for maintaining tissue integrity. In simple epithelial cells, two DM transmembrane cadherins referred to as desmoglein‐2 (Dsg2) and desmocollin‐2 (Dsc2) associate with underlying cytokeratin filaments via cytoplasmic plaque proteins. While DM regulation of epithelial mechanical properties is well established, their role in regulation of cell growth and morphogenesis is incompletely understood. Our studies were focused on defining the function of Dsc2 in simple intestinal epithelial cells (IEC). By knocking down Dsc2 with shRNA in a model IEC cell line SK‐CO15, we observed that loss of Dsc2 expression induced IEC proliferation as determined by BrdU incorporation and 3D cyst formation assays. Studies to determine the mechanism by which Dsc2 knockdown induced proliferation revealed increased activation of a small GTPase, Rap1, and down‐regulation of cell‐cell and cell‐matrix adhesion proteins JAM‐A, E‐cadherin, and β1‐integrin. Furthermore, over‐expression of Dsc2 decreased Rap1 activity. These findings support a role for Dsc2 in controlling intestinal epithelial cell adhesion and proliferation through regulation of Rap1. Supported by NIH DK‐59888 (A.N.) and CCFA fellowship award (P.N.)