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Seebohm, G.* ; Strutz-Seebohm, N.* ; Birkin, R.* ; Dell, G.* ; Bucci, C.* ; Spinosa, M.R.* ; Baltaev, R.* ; Mack, A.F.* ; Korniychuk, G.* ; Choudhury, A.* ; Marks, D.* ; Pagano, R.E.* ; Attali, B.* ; Pfeufer, A. ; Kass, RS.* ; Sanguinetti, M.C.* ; Tavare, J.M.* ; Lang, F.*

Regulation of endocytic recycling of KCNQ1/KCNE1 potassium channels.

Circ. Res. 100, 686-692 (2007)
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Stress-dependent regulation of cardiac action potential duration is mediated by the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. It is accompanied by an increased magnitude of the slow outward potassium ion current, I(Ks). KCNQ1 and KCNE1 subunits coassemble to form the I(Ks) channel. Mutations in either subunit cause long QT syndrome, an inherited cardiac arrhythmia associated with an increased risk of sudden cardiac death. Here we demonstrate that exocytosis of KCNQ1 proteins to the plasma membrane requires the small GTPase RAB11, whereas endocytosis is dependent on RAB5. We further demonstrate that RAB-dependent KCNQ1/KCNE1 exocytosis is enhanced by the serum- and glucocorticoid-inducible kinase 1, and requires phosphorylation and activation of phosphoinositide 3-phosphate 5-kinase and the generation of PI(3,5)P(2). Identification of KCNQ1/KCNE1 recycling and its modulation by serum- and glucocorticoid-inducible kinase 1-phosphoinositide 3-phosphate 5-kinase -PI(3,5)P(2) provides a mechanistic insight into stress-induced acceleration of cardiac repolarization.
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Publication type Article: Journal article
Document type Scientific Article
Keywords kinase; PIP2; RAB; trafficking; PIKfyve
ISSN (print) / ISBN 0009-7330
e-ISSN 1524-4571
Quellenangaben Volume: 100, Issue: 5, Pages: 686-692 Article Number: , Supplement: ,
Publisher Lippincott Williams & Wilkins
Reviewing status Peer reviewed