Publication Date:
2006-09-23
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579521/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579521/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Suh, Byung-Chang -- Inoue, Takanari -- Meyer, Tobias -- Hille, Bertil -- AR17803/AR/NIAMS NIH HHS/ -- GM63702/GM/NIGMS NIH HHS/ -- MH64801/MH/NIMH NIH HHS/ -- NS08174/NS/NINDS NIH HHS/ -- R01 GM030179/GM/NIGMS NIH HHS/ -- R01 GM030179-24A1/GM/NIGMS NIH HHS/ -- R01 GM030179-25/GM/NIGMS NIH HHS/ -- R01 GM063702/GM/NIGMS NIH HHS/ -- R01 MH064801/MH/NIMH NIH HHS/ -- R01 NS008174/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2006 Dec 1;314(5804):1454-7. Epub 2006 Sep 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16990515" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Calcium/metabolism
;
Cell Line
;
Cell Membrane/*metabolism
;
Diglycerides/metabolism
;
Dimerization
;
Humans
;
*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
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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