Immediate-early signaling induced by E-cadherin engagement and adhesion

Tomas D. Perez, Masako Tamada, Michael Sheetz, W. James Nelson

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Epithelial cell-cell interactions require localized adhesive interactions between E-cadherin on opposing membranes and the activation of downstream signaling pathways that affect membrane and actin dynamics. However, it is not known whether E-cadherin engagement and activation of these signaling pathways are locally coordinated or whether signaling is sustained or locally down-regulated like other receptor-mediated pathways. To obtain high spatiotemporal resolution of immediate-early signaling events upon E-cadherin engagement, we used laser tweezers to place beads coated with functional E-cadherin extracellular domain on cells. We show that cellular E-cadherin accumulated rapidly around beads, reaching a sustained plateau level in 1-3 min. Phosphoinositides and Rac1 co-accumulated with E-cadherin, reached peak levels with E-cadherin, but then rapidly dispersed. Both E-cadherin and Rac1 accumulated independently of Rac1 GTP binding/hydrolysis, but these activities were required for Rac1 dispersal. E-cadherin accumulation was dependent on membrane dynamics and actin polymerization, but actin did not stably co-accumulate with E-cadherin; mathematical modeling showed that diffusion-mediated trapping could account for the initial E-cadherin accumulation. We propose that initial E-cadherin accumulation requires active membrane dynamics and involves diffusion-mediated trapping at contact sites; to propagate further contacts, phosphatidylinositol 3-kinase and Rac1 are transiently activated by E-cadherin engagement and initiate a new round of membrane dynamics, but they are subsequently suppressed at that site to allow maintenance of weak E-cadherin mediated adhesion.

Original languageEnglish (US)
Pages (from-to)5014-5022
Number of pages9
JournalJournal of Biological Chemistry
Volume283
Issue number8
DOIs
StatePublished - Feb 22 2008
Externally publishedYes

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Cadherins
Adhesion
Membranes
Actins
Chemical activation
Phosphatidylinositol 3-Kinase
Optical Tweezers
Phosphatidylinositols
Guanosine Triphosphate
Cell Communication
Polymerization
Adhesives
Hydrolysis
Epithelial Cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Immediate-early signaling induced by E-cadherin engagement and adhesion. / Perez, Tomas D.; Tamada, Masako; Sheetz, Michael; Nelson, W. James.

In: Journal of Biological Chemistry, Vol. 283, No. 8, 22.02.2008, p. 5014-5022.

Research output: Contribution to journalArticle

Perez, Tomas D. ; Tamada, Masako ; Sheetz, Michael ; Nelson, W. James. / Immediate-early signaling induced by E-cadherin engagement and adhesion. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 8. pp. 5014-5022.
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