Publication

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

Postma, F. R., Hengeveld, T., Alblas, J., Giepmans, B. N. G., Zondag, G. C. M., Jalink, K. & Moolenaar, W. H., 9-Mar-1998, In : Journal of Cell Biology. 140, 5, p. 1199-1209 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

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

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
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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