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Activation of Gα12 regulates ectodomain shedding of cadherins in renal epithelial cells (1124.1)
Author(s) -
Xu Jen,
Wu Yong,
Li Suyang,
Hsieh YuChung,
Kong Tianqing,
Lu Tzongshi
Publication year - 2014
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.28.1_supplement.1124.1
Subject(s) - ectodomain , cadherin , autosomal dominant polycystic kidney disease , kidney , polycystic kidney disease , microbiology and biotechnology , immunostaining , downregulation and upregulation , biology , chemistry , medicine , cell , endocrinology , immunology , receptor , biochemistry , immunohistochemistry , gene , genetics
Disruption of cell‐cell and cell‐matrix adhesions in kidney epithelial cells is involved in the progression of autosomal dominant polycystic kidney disease (ADPKD). We previously showed that polycystin‐1 (PC1) inhibits activation of the G‐protein, which results in downregulation of focal adhesions. The aim of this study was to investigate whether adheren junction proteins are involved in the progression of renal cyst formation in ADPKD after Gα12 activation. Using mass spectral analysis, we first showed expression of E‐, N‐ and K‐cadherins are altered in kidney epithelial cells after Gα12 activation. Gα12 activation or Pkd1 knockout increases ectodomain shedding of E‐cadherin and N‐cadherin. In addition, the early form of N‐cadherin is increased and the late form is decreased after Gα12 activation. In renal cystic fluid collected from Pkd1 knockout mice and ADPKD patients, shed fragments from both E‐cadherin and N‐cadherin are increased but no change in K‐cadherin, which indicates a specific change of E‐cadherin and N‐cadherin by Gα12 activation. Immunostaining of kidney tissue showed that N‐cadherin is localized in nucleus after Gα12 activation, consistent with WNT/β‐catenin signaling pathway. In conclusion, our data shows that Gα12 regulates shedding of E‐cadherin and N‐cadherin and affects the cell‐cell adhesion and cell polarity of kidney epithelial cells in the development of kidney cysts in ADPKD.