Golgi and plasma membrane pools of PI(4)P contribute to plasma membrane PI(4,5)P2 and maintenance of KCNQ2/3 ion channel current

Plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] regulates the activity of many ion channels and other membrane-associated proteins. To determine precursor sources of the PM PI(4,5)P2 pool in tsA-201 cells, we monitored KCNQ2/3 channel currents and translocation of PHPLCδ1 doma...

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Published in:Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 22; p. E2281
Main Authors: Dickson, Eamonn J, Jensen, Jill B, Hille, Bertil
Format: Journal Article
Language:English
Published: United States 03.06.2014
Subjects:
1-Phosphatidylinositol 4-Kinase - metabolism
Androstadienes - pharmacology
Cell Membrane - metabolism
Cells, Cultured
Golgi Apparatus - metabolism
Humans
KCNQ2 Potassium Channel - physiology
KCNQ3 Potassium Channel - physiology
Kidney - cytology
Membrane Potentials - physiology
Myosin Type II - metabolism
Phosphatidylinositol 4,5-Diphosphate - metabolism
Phosphatidylinositols - metabolism
Protein Kinase Inhibitors - pharmacology
wortmannin
pleckstrin homology domain
phosphoinositides
ISSN:1091-6490, 1091-6490
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Summary:Plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] regulates the activity of many ion channels and other membrane-associated proteins. To determine precursor sources of the PM PI(4,5)P2 pool in tsA-201 cells, we monitored KCNQ2/3 channel currents and translocation of PHPLCδ1 domains as real-time indicators of PM PI(4,5)P2, and translocation of PHOSH2×2, and PHOSH1 domains as indicators of PM and Golgi phosphatidylinositol 4-phosphate [PI(4)P], respectively. We selectively depleted PI(4)P pools at the PM, Golgi, or both using the rapamycin-recruitable lipid 4-phosphatases. Depleting PI(4)P at the PM with a recruitable 4-phosphatase (Sac1) results in a decrease of PI(4,5)P2 measured by electrical or optical indicators. Depleting PI(4)P at the Golgi with the 4-phosphatase or disrupting membrane-transporting motors induces a decline in PM PI(4,5)P2. Depleting PI(4)P simultaneously at both the Golgi and the PM induces a larger decrease of PI(4,5)P2. The decline of PI(4,5)P2 following 4-phosphatase recruitment takes 1-2 min. Recruiting the endoplasmic reticulum (ER) toward the Golgi membranes mimics the effects of depleting PI(4)P at the Golgi, apparently due to the trans actions of endogenous ER Sac1. Thus, maintenance of the PM pool of PI(4,5)P2 appears to depend on precursor pools of PI(4)P both in the PM and in the Golgi. The decrease in PM PI(4,5)P2 when Sac1 is recruited to the Golgi suggests that the Golgi contribution is ongoing and that PI(4,5)P2 production may be coupled to important cell biological processes such as membrane trafficking or lipid transfer activity.
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ISSN:1091-6490
1091-6490
DOI:10.1073/pnas.1407133111