Home LiteratureArticle Details
PMID: 16990515 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Rapid chemically induced changes of PtdIns(4,5)P2 gate KCNQ ion channels.

Science (New York, N.Y.) ·Vol. 314 ·No. 5804 ·2006-12-01 ·Pages 1454-7

Suh BC, Inoue T, Meyer T, Hille B

Abstract

To resolve the controversy about messengers regulating KCNQ ion channels during phospholipase C-mediated suppression of current, we designed translocatable enzymes that quickly alter the phosphoinositide composition of the plasma membrane after application of a chemical cue. The KCNQ current falls rapidly to zero when phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2 or PI(4,5)P2] is depleted without changing Ca2+, diacylglycerol, or inositol 1,4,5-trisphosphate. Current rises by 30% when PI(4,5)P2 is overproduced and does not change when phosphatidylinositol 3,4,5-trisphosphate is raised. Hence, the depletion of PI(4,5)P2 suffices to suppress current fully, and other second messengers are not needed. Our approach is ideally suited to study biological signaling networks involving membrane phosphoinositides.

MeSH Terms
Animals Calcium/metabolism Cell Line Cell Membrane/metabolism Diglycerides/metabolism Dimerization Humans Inositol Polyphosphate 5-Phosphatases Ion Channel Gating KCNQ Potassium Channels/metabolism KCNQ2 Potassium Channel/metabolism KCNQ3 Potassium Channel/metabolism Mice NIH 3T3 Cells Oxotremorine/analogs & derivatives,pharmacology Phosphatidylinositol 4,5-Diphosphate/metabolism Phosphoric Monoester Hydrolases/metabolism Phosphorylation Recombinant Fusion Proteins/metabolism Second Messenger Systems Sirolimus/analogs & derivatives,pharmacology
Chemicals
Diglycerides KCNQ Potassium Channels KCNQ2 Potassium Channel KCNQ3 Potassium Channel Phosphatidylinositol 4,5-Diphosphate Recombinant Fusion Proteins Oxotremorine oxotremorine M Phosphoric Monoester Hydrolases Inositol Polyphosphate 5-Phosphatases Calcium Sirolimus
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Suh Byung-Chang
Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195, USA.
Inoue Takanari
Meyer Tobias
Hille Bertil
References (25)
25 references, click to expand
  1. Controlling signal transduction with synthetic ligands.
    Science. 1993 Nov 12;262(5136):1019-24 PMID: 7694365
  2. PDGF-dependent tyrosine phosphorylation stimulates production of novel polyphosphoinositides in intact cells.
    Cell. 1989 Apr 7;57(1):167-75 PMID: 2467744
  3. Ras-dependent induction of cellular responses by constitutively active phosphatidylinositol-3 kinase.
    Science. 1995 Apr 7;268(5207):100-2 PMID: 7701328
  4. Receptor-induced transient reduction in plasma membrane PtdIns(4,5)P2 concentration monitored in living cells.
    Curr Biol. 1998 Mar 12;8(6):343-6 PMID: 9512420
  5. Type I phosphatidylinositol-4-phosphate 5-kinases. Cloning of the third isoform and deletion/substitution analysis of members of this novel lipid kinase family.
    J Biol Chem. 1998 Apr 10;273(15):8741-8 PMID: 9535851
  6. Tyrosine 1101 of Tie2 is the major site of association of p85 and is required for activation of phosphatidylinositol 3-kinase and Akt.
    Mol Cell Biol. 1998 Jul;18(7):4131-40 PMID: 9632797
  7. Protein kinase C as a molecular machine for decoding calcium and diacylglycerol signals.
    Cell. 1998 Oct 30;95(3):307-18 PMID: 9814702
  8. Spatiotemporal dynamics of inositol 1,4,5-trisphosphate that underlies complex Ca2+ mobilization patterns.
    Science. 1999 May 28;284(5419):1527-30 PMID: 10348740
  9. Relationship between membrane phosphatidylinositol-4,5-bisphosphate and receptor-mediated inhibition of native neuronal M channels.
    J Neurosci. 2005 Mar 30;25(13):3400-13 PMID: 15800195
  10. An inducible translocation strategy to rapidly activate and inhibit small GTPase signaling pathways.
    Nat Methods. 2005 Jun;2(6):415-8 PMID: 15908919
  11. Regulation of ion channels by phosphatidylinositol 4,5-bisphosphate.
    Curr Opin Neurobiol. 2005 Jun;15(3):370-8 PMID: 15922587
  12. Ion channel defects in idiopathic epilepsies.
    Curr Pharm Des. 2005;11(21):2737-52 PMID: 16101452
  13. Phospholipase C in living cells: activation, inhibition, Ca2+ requirement, and regulation of M current.
    J Gen Physiol. 2005 Sep;126(3):243-62 PMID: 16129772
  14. Regulation of Kv7 (KCNQ) K+ channel open probability by phosphatidylinositol 4,5-bisphosphate.
    J Neurosci. 2005 Oct 26;25(43):9825-35 PMID: 16251430
  15. Pathways modulating neural KCNQ/M (Kv7) potassium channels.
    Nat Rev Neurosci. 2005 Nov;6(11):850-62 PMID: 16261179
  16. PI(3,4,5)P3 and PI(4,5)P2 lipids target proteins with polybasic clusters to the plasma membrane.
    Science. 2006 Dec 1;314(5804):1458-61 PMID: 17095657
  17. Distinct specificities of inwardly rectifying K(+) channels for phosphoinositides.
    J Biol Chem. 1999 Dec 17;274(51):36065-72 PMID: 10593888
  18. 1-Phosphatidylinositol 3-kinase activity is required for insulin-stimulated glucose transport but not for RAS activation in CHO cells.
    Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7415-9 PMID: 8052599
  19. Phosphatidylinositol 4,5-bisphosphate functions as a second messenger that regulates cytoskeleton-plasma membrane adhesion.
    Cell. 2000 Jan 21;100(2):221-8 PMID: 10660045
  20. Specificity determinants in phosphoinositide dephosphorylation: crystal structure of an archetypal inositol polyphosphate 5-phosphatase.
    Cell. 2001 May 4;105(3):379-89 PMID: 11348594
  21. The complex and intriguing lives of PIP2 with ion channels and transporters.
    Sci STKE. 2001 Dec 4;2001(111):re19 PMID: 11734659
  22. The phosphoinositide 3-kinase pathway.
    Science. 2002 May 31;296(5573):1655-7 PMID: 12040186
  23. Recovery from muscarinic modulation of M current channels requires phosphatidylinositol 4,5-bisphosphate synthesis.
    Neuron. 2002 Aug 1;35(3):507-20 PMID: 12165472
  24. Type I gamma phosphatidylinositol phosphate kinase targets and regulates focal adhesions.
    Nature. 2002 Nov 7;420(6911):89-93 PMID: 12422220
  25. Regulation of KCNQ2/KCNQ3 current by G protein cycling: the kinetics of receptor-mediated signaling by Gq.
    J Gen Physiol. 2004 Jun;123(6):663-83 PMID: 15173220
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1131163
Published
2006-12-01
Epub
2006-00-21
Pages
1454-7
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3579521
Subset
IM
Grants
NINDS NIH HHS · R01 NS008174 · United States
NIMH NIH HHS · R01 MH064801 · United States
NINDS NIH HHS · NS08174 · United States
NINDS NIH HHS · R37 NS008174 · United States
NIGMS NIH HHS · R01 GM063702 · United States
NIMH NIH HHS · MH64801 · United States
NIAMS NIH HHS · R01 AR017803 · United States
NIGMS NIH HHS · GM63702 · United States
NIAMS NIH HHS · AR17803 · United States
NIGMS NIH HHS · R01 GM030179-24A1 · United States
NIGMS NIH HHS · R01 GM030179 · United States
NIGMS NIH HHS · R01 GM030179-25 · United States
Corrections
CommentIn
PMID: 17095656
External Links
PubMed source DOI: 10.1126/science.1131163 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2