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Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate

van Zeijl, L., Ponsioen, B., Giepmans, B. N. G., Ariaens, A., Postma, F. R., Várnai, P., Balla, T., Divecha, N., Jalink, K. & Moolenaar, W. H., 4-Jun-2007, In : Journal of Cell Biology. 177, 5, p. 881-891 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Leonie van Zeijl
  • Bas Ponsioen
  • Ben N. G. Giepmans
  • Aafke Ariaens
  • Friso R. Postma
  • Péter Várnai
  • Tamas Balla
  • Nullin Divecha
  • Kees Jalink
  • Wouter H Moolenaar

Cell-cell communication through connexin43 (Cx43)-based gap junction channels is rapidly inhibited upon activation of various G protein coupled receptors; however, the mechanism is unknown. We show that Cx43-based cell-cell communication is inhibited by depletion of phosphatidylinositol 4,5-bisphosphate (PtdIns[4,5] P-2) from the plasma membrane. Knockdown of phospholipase C beta 3 (PLC beta 3) inhibits PtdIns(4,5) P2 hydrolysis and keeps Cx43 channels open after receptor activation. Using a translocatable 5-phosphatase, we show that PtdIns(4,5) P2 depletion is sufficient to close Cx43 channels. When PtdIns(4,5) P2 is overproduced by PtdIns(4)P 5-kinase, Cx43 channel closure is impaired. We. nd that the Cx43 binding partner zona occludens 1 (ZO-1) interacts with PLC beta 3 via its third PDZ domain. ZO-1 is essential for PtdIns(4,5) P-2-hydrolyzing receptors to inhibit cell-cell communication, but not for receptor PLC coupling. Our results show that PtdIns(4,5) P-2 is a key regulator of Cx43 channel function, with no role for other second messengers, and suggest that ZO-1 assembles PLC beta 3 and Cx43 into a signaling complex to allow regulation of cell-cell communication by localized changes in PtdIns(4,5) P2.

Original languageEnglish
Pages (from-to)881-891
Number of pages11
JournalJournal of Cell Biology
Volume177
Issue number5
Publication statusPublished - 4-Jun-2007

    Keywords

  • CELL-CELL COMMUNICATION, INTERCELLULAR COMMUNICATION, PROTEIN CONNEXIN-43, PHOSPHOLIPASE-C, LIVING CELLS, ION CHANNELS, WOUND REPAIR, PHOSPHORYLATION, ACTIVATION, RECEPTORS

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