Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2015 Dec 29;11252:E7286-92. doi: 10.1073/pnas.1516238112.
Show Gene links
Show Anatomy links
KCNE3 acts by promoting voltage sensor activation in KCNQ1.
Barro-Soria R
,
Perez ME
,
Larsson HP
.
???displayArticle.abstract???
KCNE β-subunits assemble with and modulate the properties of voltage-gated K(+) channels. In the colon, stomach, and kidney, KCNE3 coassembles with the α-subunit KCNQ1 to form K(+) channels important for K(+) and Cl(-) secretion that appear to be voltage-independent. How KCNE3 subunits turn voltage-gated KCNQ1 channels into apparent voltage-independent KCNQ1/KCNE3 channels is not completely understood. Different mechanisms have been proposed to explain the effect of KCNE3 on KCNQ1 channels. Here, we use voltage clamp fluorometry to determine how KCNE3 affects the voltage sensor S4 and the gate of KCNQ1. We find that S4 moves in KCNQ1/KCNE3 channels, and that inward S4 movement closes the channel gate. However, KCNE3 shifts the voltage dependence of S4 movement to extreme hyperpolarized potentials, such that in the physiological voltage range, the channel is constitutively conducting. By separating S4 movement and gate opening, either by a mutation or PIP2 depletion, we show that KCNE3 directly affects the S4 movement in KCNQ1. Two negatively charged residues of KCNE3 (D54 and D55) are found essential for the effect of KCNE3 on KCNQ1 channels, mainly exerting their effects by an electrostatic interaction with R228 in S4. Our results suggest that KCNE3 primarily affects the voltage-sensing domain and only indirectly affects the gate.
Aggarwal,
Contribution of the S4 segment to gating charge in the Shaker K+ channel.
1996, Pubmed,
Xenbase
Aggarwal,
Contribution of the S4 segment to gating charge in the Shaker K+ channel.
1996,
Pubmed
,
Xenbase
Angelo,
KCNE5 induces time- and voltage-dependent modulation of the KCNQ1 current.
2002,
Pubmed
,
Xenbase
Barhanin,
K(V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current.
1996,
Pubmed
,
Xenbase
Boulet,
Role of the S6 C-terminus in KCNQ1 channel gating.
2007,
Pubmed
Choi,
A shared mechanism for lipid- and beta-subunit-coordinated stabilization of the activated K+ channel voltage sensor.
2010,
Pubmed
,
Xenbase
Chowdhury,
Free-energy relationships in ion channels activated by voltage and ligand.
2013,
Pubmed
Chung,
Location of KCNE1 relative to KCNQ1 in the I(KS) potassium channel by disulfide cross-linking of substituted cysteines.
2009,
Pubmed
Grahammer,
The cardiac K+ channel KCNQ1 is essential for gastric acid secretion.
2001,
Pubmed
Grahammer,
The small conductance K+ channel, KCNQ1: expression, function, and subunit composition in murine trachea.
2001,
Pubmed
Jespersen,
The KCNQ1 potassium channel: from gene to physiological function.
2005,
Pubmed
Kosek,
The global burden of diarrhoeal disease, as estimated from studies published between 1992 and 2000.
2003,
Pubmed
Kunzelmann,
Electrolyte transport in the mammalian colon: mechanisms and implications for disease.
2002,
Pubmed
Kuruma,
A hyperpolarization- and acid-activated nonselective cation current in Xenopus oocytes.
2000,
Pubmed
,
Xenbase
Lai,
Denaturing high-performance liquid chromatography screening of the long QT syndrome-related cardiac sodium and potassium channel genes and identification of novel mutations and single nucleotide polymorphisms.
2005,
Pubmed
Larsson,
Transmembrane movement of the shaker K+ channel S4.
1996,
Pubmed
,
Xenbase
Lerche,
Chromanol 293B binding in KCNQ1 (Kv7.1) channels involves electrostatic interactions with a potassium ion in the selectivity filter.
2007,
Pubmed
,
Xenbase
Li,
KCNE1 enhances phosphatidylinositol 4,5-bisphosphate (PIP2) sensitivity of IKs to modulate channel activity.
2011,
Pubmed
,
Xenbase
Lohrmann,
A new class of inhibitors of cAMP-mediated Cl- secretion in rabbit colon, acting by the reduction of cAMP-activated K+ conductance.
1995,
Pubmed
Long,
Voltage sensor of Kv1.2: structural basis of electromechanical coupling.
2005,
Pubmed
Lundby,
KCNE3 mutation V17M identified in a patient with lone atrial fibrillation.
2008,
Pubmed
,
Xenbase
Mannuzzu,
Direct physical measure of conformational rearrangement underlying potassium channel gating.
1996,
Pubmed
,
Xenbase
Melman,
Structural determinants of KvLQT1 control by the KCNE family of proteins.
2001,
Pubmed
Melman,
KCNE1 binds to the KCNQ1 pore to regulate potassium channel activity.
2004,
Pubmed
Nakajo,
KCNE1 and KCNE3 stabilize and/or slow voltage sensing S4 segment of KCNQ1 channel.
2007,
Pubmed
,
Xenbase
Nerbonne,
Molecular physiology of cardiac repolarization.
2005,
Pubmed
Ohno,
Novel KCNE3 mutation reduces repolarizing potassium current and associated with long QT syndrome.
2009,
Pubmed
Osteen,
Allosteric gating mechanism underlies the flexible gating of KCNQ1 potassium channels.
2012,
Pubmed
,
Xenbase
Osteen,
KCNE1 alters the voltage sensor movements necessary to open the KCNQ1 channel gate.
2010,
Pubmed
,
Xenbase
Panaghie,
Interaction of KCNE subunits with the KCNQ1 K+ channel pore.
2006,
Pubmed
,
Xenbase
Panaghie,
The role of S4 charges in voltage-dependent and voltage-independent KCNQ1 potassium channel complexes.
2007,
Pubmed
,
Xenbase
Ranganathan,
Spatial localization of the K+ channel selectivity filter by mutant cycle-based structure analysis.
1996,
Pubmed
Rocheleau,
KCNE peptides differently affect voltage sensor equilibrium and equilibration rates in KCNQ1 K+ channels.
2008,
Pubmed
,
Xenbase
Rosengren,
Reduced insulin exocytosis in human pancreatic β-cells with gene variants linked to type 2 diabetes.
2012,
Pubmed
Sand,
Deep resequencing of the voltage-gated potassium channel subunit KCNE3 gene in chronic tinnitus.
2011,
Pubmed
Sanguinetti,
Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel.
1996,
Pubmed
,
Xenbase
Schroeder,
A constitutively open potassium channel formed by KCNQ1 and KCNE3.
2000,
Pubmed
,
Xenbase
Seoh,
Voltage-sensing residues in the S2 and S4 segments of the Shaker K+ channel.
1996,
Pubmed
,
Xenbase
Tai,
The conduction pore of a cardiac potassium channel.
1998,
Pubmed
,
Xenbase
Takumi,
Cloning of a membrane protein that induces a slow voltage-gated potassium current.
1988,
Pubmed
,
Xenbase
Teng,
Novel gene hKCNE4 slows the activation of the KCNQ1 channel.
2003,
Pubmed
,
Xenbase
Tinel,
KCNE2 confers background current characteristics to the cardiac KCNQ1 potassium channel.
2000,
Pubmed
,
Xenbase
Torekov,
KCNQ1 long QT syndrome patients have hyperinsulinemia and symptomatic hypoglycemia.
2014,
Pubmed
Wang,
Functional significance of K+ channel β-subunit KCNE3 in auditory neurons.
2014,
Pubmed
Xu,
KCNQ1 and KCNE1 in the IKs channel complex make state-dependent contacts in their extracellular domains.
2008,
Pubmed
,
Xenbase
Yang,
Molecular basis of charge movement in voltage-gated sodium channels.
1996,
Pubmed
Zaydman,
Kv7.1 ion channels require a lipid to couple voltage sensing to pore opening.
2013,
Pubmed
,
Xenbase
Zaydman,
Domain-domain interactions determine the gating, permeation, pharmacology, and subunit modulation of the IKs ion channel.
2014,
Pubmed
,
Xenbase
