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

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

Research output: Contribution to journalArticle

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Abstract

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]P2) from the plasma membrane. Knockdown of phospholipase Cβ3 (PLCβ3) 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 find that the Cx43 binding partner zona occludens 1 (ZO-1) interacts with PLCβ3 via its third PDZ domain. ZO-1 is essential for PtdIns(4,5)P2-hydrolyzing receptors to inhibit cell-cell communication, but not for receptor-PLC coupling. Our results show that PtdIns(4,5)P2 is a key regulator of Cx43 channel function, with no role for other second messengers, and suggest that ZO-1 assembles PLCβ3 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
DOIs
Publication statusPublished - Jun 4 2007

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Connexin 43
Phosphatidylinositol 4,5-Diphosphate
Phosphatidylinositols
Cell Communication
Phospholipases
Herpes Zoster
phosphoinositide 5-phosphatase
PDZ Domains
Gap Junctions
Second Messenger Systems
G-Protein-Coupled Receptors
Hydrolysis
Cell Membrane

ASJC Scopus subject areas

  • Cell Biology

Cite this

Van Zeijl, L., Ponsioen, B., Giepmans, B. N. G., Ariaens, A., Postma, F. R., Várnai, P., ... Moolenaar, W. H. (2007). Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate. Journal of Cell Biology, 177(5), 881-891. https://doi.org/10.1083/jcb.200610144

Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate. / Van Zeijl, Leonie; Ponsioen, Bas; Giepmans, Ben N G; Ariaens, Aafke; Postma, Friso R.; Várnai, P.; Balla, Tamas; Divecha, Nullin; Jalink, Kees; Moolenaar, Wouter H.

In: Journal of Cell Biology, Vol. 177, No. 5, 04.06.2007, p. 881-891.

Research output: Contribution to journalArticle

Van Zeijl, L, Ponsioen, B, Giepmans, BNG, Ariaens, A, Postma, FR, Várnai, P, Balla, T, Divecha, N, Jalink, K & Moolenaar, WH 2007, 'Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate', Journal of Cell Biology, vol. 177, no. 5, pp. 881-891. https://doi.org/10.1083/jcb.200610144
Van Zeijl, Leonie ; Ponsioen, Bas ; Giepmans, Ben N G ; Ariaens, Aafke ; Postma, Friso R. ; Várnai, P. ; Balla, Tamas ; Divecha, Nullin ; Jalink, Kees ; Moolenaar, Wouter H. / Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate. In: Journal of Cell Biology. 2007 ; Vol. 177, No. 5. pp. 881-891.
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