Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate
Open Access
- 29 May 2007
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 177 (5), 881-891
- https://doi.org/10.1083/jcb.200610144
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.Keywords
This publication has 64 references indexed in Scilit:
- Direct measurement of cyclic AMP diffusion and signaling through connexin43 gap junctional channelsExperimental Cell Research, 2007
- Rapid Chemically Induced Changes of PtdIns(4,5)P 2 Gate KCNQ Ion ChannelsScience, 2006
- Rapidly inducible changes in phosphatidylinositol 4,5-bisphosphate levels influence multiple regulatory functions of the lipid in intact living cellsThe Journal of cell biology, 2006
- Pasteurella multocida Toxin-induced Activation of RhoA Is Mediated via Two Families of Gα Proteins, Gαq and Gα12/13Online Journal of Public Health Informatics, 2005
- Establishment and Characterization of Cultured Epithelial Cells Lacking Expression of ZO-1Online Journal of Public Health Informatics, 2004
- Connexin disorders of the ear, skin, and lensBiochimica et Biophysica Acta (BBA) - Biomembranes, 2004
- The Roles of PDZ-Containing Proteins in PLC-β-Mediated SignalingBiochemical and Biophysical Research Communications, 2001
- Monitoring Agonist-induced Phospholipase C Activation in Live Cells by Fluorescence Resonance Energy TransferOnline Journal of Public Health Informatics, 2001
- Regulation and Intracellular Trafficking Pathways of the Endothelin ReceptorsOnline Journal of Public Health Informatics, 2000
- Subtype-Specific Desensitization of Human Endothelin ETA and ETB Receptors Reflects Differential Receptor PhosphorylationBiochemistry, 1997