Open AccessMechanical disruption of E-cadherin complexes with epidermal growth factor receptor actuates growth factor–dependent signaling
Author(s) -
Brendan G. Sullivan,
Taylor P. Light,
Vinh Vu,
Adrian Kapustka,
Kalina Hristova,
Deborah Leckband
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2100679119
Subject(s) - epidermal growth factor receptor , cadherin , microbiology and biotechnology , heterotrimeric g protein , epidermal growth factor , signal transduction , chemistry , biology , receptor , biophysics , cell , biochemistry , g protein
Significance Force transduction at interepithelial junctions involves E-cadherin–mediated activation of epidermal growth factor receptor (EGFR) signaling, which modulates local cytoskeletal remodeling and cell proliferation. Findings show that E-cadherin and EGFR form a heteroreceptor complex at the membrane. Increased tension on E-cadherin bonds disrupts the complex in the absence of epidermal growth factor (EGF), but the mechanical activation of EGFR signaling requires soluble EGF. Fully quantified spectral imaging fluorescence resonance energy transfer measurements further revealed that E-cadherin and EGFR form a heterotrimeric complex at the plasma membrane, comprising two E-cadherins bound to an EGFR monomer. These results suggest that tugging forces on E-cadherin adhesions activate force transduction cascades, by releasing EGFR monomers from the complex, to enable EGFR to homodimerize, bind EGF, and signal.