Regulation of endocytic recycling of KCNQ1/KCNE1 potassium channels.
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.
Seebohm
Guiscard
G
Department of Physiology I, University of Tuebingen, Gmelinstrasse 5, D-72076 Tuebingen, Germany. guiscard.seebohm@gmx.de
Strutz-Seebohm
Nathalie
N
Birkin
Ria
R
Dell
Ghislaine
G
Bucci
Cecilia
C
Spinosa
Maria R
MR
Baltaev
Ravshan
R
Mack
Andreas F
AF
Korniychuk
Ganna
G
Choudhury
Amit
A
Marks
David
D
Pagano
Richard E
RE
Attali
Bernard
B
Pfeufer
Arne
A
Kass
Robert S
RS
Sanguinetti
Michael C
MC
Tavare
Jeremy M
JM
Lang
Florian
F
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
C489622:KCNE1 protein, human; D051657:KCNQ1 Potassium Channel; D024642:Potassium Channels, Voltage-Gated