title: Regulation of endocytic recycling of KCNQ1/KCNE1 potassium channels.
abstract: 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.
authors.affiliation: Department of Physiology I, University of Tuebingen, Gmelinstrasse 5, D-72076 Tuebingen, Germany. guiscard.seebohm@gmx.de
authors.forename: Guiscard
authors.initials: G
authors.lastname: Seebohm
authors.forename: Nathalie
authors.initials: N
authors.lastname: Strutz-Seebohm
authors.forename: Ria
authors.initials: R
authors.lastname: Birkin
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Dell
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bucci
authors.forename: Maria R
authors.initials: MR
authors.lastname: Spinosa
authors.forename: Ravshan
authors.initials: R
authors.lastname: Baltaev
authors.forename: Andreas F
authors.initials: AF
authors.lastname: Mack
authors.forename: Ganna
authors.initials: G
authors.lastname: Korniychuk
authors.forename: Amit
authors.initials: A
authors.lastname: Choudhury
authors.forename: David
authors.initials: D
authors.lastname: Marks
authors.forename: Richard E
authors.initials: RE
authors.lastname: Pagano
authors.forename: Bernard
authors.initials: B
authors.lastname: Attali
authors.forename: Arne
authors.initials: A
authors.lastname: Pfeufer
authors.forename: Robert S
authors.initials: RS
authors.lastname: Kass
authors.forename: Michael C
authors.initials: MC
authors.lastname: Sanguinetti
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Tavare
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004705:Endocytosis / Q000502:physiology*; D005089:Exocytosis / Q000502:physiology; D005260:Female; D015640:Ion Channel Gating / Q000502:physiology; D051657:KCNQ1 Potassium Channel / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D022161:Transport Vesicles / Q000378:metabolism*; D014981:Xenopus
chemical_list: C489622:KCNE1 protein, human; D051657:KCNQ1 Potassium Channel; D024642:Potassium Channels, Voltage-Gated