Enhanced interaction between focal adhesion and adherens junction proteins: Involvement in sphingosine 1-phosphate-induced endothelial barrier enhancement

Xiaoguang Sun, Yasushi Shikata, Lichun Wang, Kazuyoshi Ohmori, Naoko Watanabe, Jun Wada, Kenichi Shikata, Konstantin G. Birukov, Hirofumi Makino, Jeffrey R. Jacobson, Steven M. Dudek, Joe G.N. Garcia

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Sphingosine 1-phosphate (S1P) is an important vascular barrier regulatory agonist which enhances the junctional integrity of human lung endothelial cell monolayers. We have now demonstrated that S1P induced cortical actin ring formation and redistribution of focal adhesion kinase (FAK) and paxillin to the cell periphery suggesting the critical role of cell-cell adhesion in endothelial barrier enhancement. Co-immunoprecipitation studies revealed increased association of VE-cadherin with FAK and paxillin in S1P-challenged human pulmonary artery endothelial cell (HPAEC) monolayers. Furthermore, S1P-induced enhancement of VE-cadherin interaction with α-catenin and β-catenin was associated with the increased formation of FAK-β-catenin protein complexes. Depletion of β-catenin (siRNA) resulted in loss of S1P-mediated VE-cadherin association with FAK and paxillin rearrangement. Furthermore, transendothelial electrical resistance (an index of barrier function) demonstrated that β-catenin siRNA significantly attenuated S1P-induced barrier enhancement. These results demonstrate a mechanism of S1P-induced endothelial barrier enhancement via β-catenin-linked adherens junction and focal adhesion interaction.

Original languageEnglish (US)
Pages (from-to)304-313
Number of pages10
JournalMicrovascular Research
Volume77
Issue number3
DOIs
StatePublished - May 2009

Keywords

  • Adherens junction
  • Endothelial
  • F-actin
  • Focal adhesion
  • Focal adhesion kinase
  • Paxillin
  • Sphingosine 1-phosphate
  • VE-cadherin
  • α-catenin
  • β-catenin

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

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    Sun, X., Shikata, Y., Wang, L., Ohmori, K., Watanabe, N., Wada, J., Shikata, K., Birukov, K. G., Makino, H., Jacobson, J. R., Dudek, S. M., & Garcia, J. G. N. (2009). Enhanced interaction between focal adhesion and adherens junction proteins: Involvement in sphingosine 1-phosphate-induced endothelial barrier enhancement. Microvascular Research, 77(3), 304-313. https://doi.org/10.1016/j.mvr.2008.12.004