Acute loss of cell-cell communication caused by G protein-coupled receptors: a critical role for c-Src

Friso R. Postma, Trudi Hengeveld, Jacqueline Alblas, Ben N. G. Giepmans, Gerben C. M. Zondag, Kees Jalink, Wouter H. Moolenaar

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Abstract

Gap junctions mediate cell-cell communication in almost all tissues, but little is known about their regulation by physiological stimuli. Using a novel single-electrode technique, together with dye coupling studies, we show that in cells expressing gap junction protein connexin43, cell-cell communication is rapidly disrupted by G protein-coupled receptor agonists, notably lysophosphatidic acid, thrombin, and neuropeptides. In the continuous presence of agonist, junctional communication fully recovers within 1-2 h of receptor stimulation. In contrast, a desensitization-defective G protein-coupled receptor mediates prolonged uncoupling, indicating that recovery of communication is controlled, at least in part, by receptor desensitization. Agonist-induced gap junction closure consistently follows inositol lipid breakdown and membrane depolarization and coincides with Rho-mediated cytoskeletal remodeling. However, we find that gap junction closure is independent of Ca2+, protein kinase C, mitogen-activated protein kinase, or membrane potential, and requires neither Rho nor Ras activation. Gap junction closure is prevented by tyrphostins, by dominant-negative c-Src, and in Src-deficient cells. Thus, G protein-coupled receptors use a Src tyrosine kinase pathway to transiently inhibit connexin43-based cell-cell communication.

Original languageEnglish
Pages (from-to)1199-1209
Number of pages11
JournalJournal of Cell Biology
Volume140
Issue number5
DOIs
Publication statusPublished - 9-Mar-1998

Keywords

  • Animals
  • Cell Communication
  • Cell Line
  • Connexin 43
  • Electrodes
  • GTP-Binding Proteins
  • HeLa Cells
  • Humans
  • Mice
  • Patch-Clamp Techniques
  • Protein-Tyrosine Kinases
  • Rats
  • Receptors, Cell Surface
  • Signal Transduction
  • src-Family Kinases

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