DDR1 regulates the stabilization of cell surface E-cadherin and E-cadherin-mediated cell aggregation

Rajalakshmanan Eswaramoorthy, Chih Kuang Wang, Wen Cheng Chen, Ming Jer Tang, Mei Ling Ho, Chi Ching Hwang, Hui Min Wang, Chau Zen Wang

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

The stabilization of cell surface E-cadherin is important for the maintenance of apical junction complexes and epithelial polarity. Previously, we reported that discoidin domain receptor 1 (DDR1) forms a complex with E-cadherin at adhesive contacts; however, the regulatory role of DDR1 in the stabilization of cell surface E-cadherin and E-cadherin-mediated cell behaviors remained undefined. To gain insight into these questions, we utilized two stable clones depleted for DDR1 via the small interfering RNA (siRNA) technique, and we over-expressed DDR1 in MDCK cells. We performed Western blotting, immunofluorescence analysis, flow cytometry, and cell aggregation studies to investigate the effect of DDR1 on cell surface E-cadherin. The results showed that both DDR1/2 and E-cadherin use their extracellular domains to form DDR/E-cadherin complexes. Neither the depletion nor the over-expression of DDR1 changed the expression level of E-cadherin in MDCK cells. Collagen disrupted the formation of E-cadherin complexes and caused E-cadherin to accumulate in the cytoplasm; however, over-expression of DDR1 stabilized E-cadherin on the cell surface and decreased its cytoplasmic accumulation. Furthermore, independently of collagen stimulation, the depletion of DDR1 resulted in a decrease in the level of cell surface E-cadherin, which consequently caused its cytoplasmic accumulation and decreased E-cadherin-mediated cell aggregation. These results indicate that DDR1 can increase the stability of cell surface E-cadherin and promote MDCK cell aggregation, which may be mediated through the formation of DDR1/E-cadherin complexes. Overall, these findings have implications for the physiological roles of DDR1 in association with the maintenance of both the adhesion junction and epithelial polarity.

Original languageEnglish
Pages (from-to)387-397
Number of pages11
JournalJournal of Cellular Physiology
Volume224
Issue number2
DOIs
Publication statusPublished - 2010 Aug 1

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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