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.
Biophys J
2010 Jun 16;9812:2867-76. doi: 10.1016/j.bpj.2010.03.044.
Show Gene links
Show Anatomy links
Functional rescue of Kv4.3 channel tetramerization mutants by KChIP4a.
Liang P
,
Chen H
,
Cui Y
,
Lei L
,
Wang K
.
???displayArticle.abstract???
KChIP4a shows a high homology with other members of the family of Kv channel-interacting proteins (KChIPs) in the conserved C-terminal core region, but exhibits a unique modulation of Kv4 channel gating and surface expression. Unlike KChIP1, the KChIP4 splice variant KChIP4a has been shown to inhibit surface expression and function as a suppressor of channel inactivation of Kv4. In this study, we sought to determine whether the multitasking KChIP4a modulates Kv4 function in a clamping fashion similar to that shown by KChIP1. Injection of Kv4.3 T1 zinc mutants into Xenopus oocytes resulted in the nonfunctional expression of Kv4.3 channels. Coexpression of Kv4.3 zinc mutants with WT KChIP4a gave rise to the functional expression of Kv4.3 current. Oocyte surface labeling results confirm the correlation between functional rescue and enhanced surface expression of zinc mutant proteins. Chimeric mutations that replace the Kv4.3 N-terminus with N-terminal KChIP4a or N-terminal deletion of KChIP4a further demonstrate that the functional rescue of Kv4.3 channel tetramerization mutants depends on the KChIP4a core region, but not its N-terminus. Structure-guided mutation of two critical residues of core KChIP4a attenuated functional rescue and tetrameric assembly. Moreover, size exclusion chromatography combined with fast protein liquid chromatography showed that KChIP4a can drive zinc mutant monomers to assemble as tetramers. Taken together, our results show that KChIP4a can rescue the function of tetramerization-defective Kv4 monomers. Therefore, we propose that core KChIP4a functions to promote tetrameric assembly and enhance surface expression of Kv4 channels by a clamping action, whereas its N-terminus inhibits surface expression of Kv4 by a mechanism that remains elusive.
An,
Modulation of A-type potassium channels by a family of calcium sensors.
2000, Pubmed,
Xenbase
An,
Modulation of A-type potassium channels by a family of calcium sensors.
2000,
Pubmed
,
Xenbase
Beck,
Remodelling inactivation gating of Kv4 channels by KChIP1, a small-molecular-weight calcium-binding protein.
2002,
Pubmed
,
Xenbase
Bixby,
Zn2+-binding and molecular determinants of tetramerization in voltage-gated K+ channels.
1999,
Pubmed
Bähring,
Conserved Kv4 N-terminal domain critical for effects of Kv channel-interacting protein 2.2 on channel expression and gating.
2001,
Pubmed
Cai,
Unique roles of SK and Kv4.2 potassium channels in dendritic integration.
2004,
Pubmed
Cui,
Enhanced trafficking of tetrameric Kv4.3 channels by KChIP1 clamping.
2008,
Pubmed
,
Xenbase
Deng,
Identification of the alternative promoters of the KChIP4 subfamily.
2005,
Pubmed
Dilks,
Cloning and expression of the human kv4.3 potassium channel.
1999,
Pubmed
,
Xenbase
Gebauer,
N-type inactivation features of Kv4.2 channel gating.
2004,
Pubmed
Guo,
Role of heteromultimers in the generation of myocardial transient outward K+ currents.
2002,
Pubmed
Hoffman,
K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons.
1997,
Pubmed
Holmqvist,
Kinetic modulation of Kv4-mediated A-current by arachidonic acid is dependent on potassium channel interacting proteins.
2001,
Pubmed
,
Xenbase
Holmqvist,
Elimination of fast inactivation in Kv4 A-type potassium channels by an auxiliary subunit domain.
2002,
Pubmed
,
Xenbase
Jerng,
Multiple Kv channel-interacting proteins contain an N-terminal transmembrane domain that regulates Kv4 channel trafficking and gating.
2008,
Pubmed
Johnston,
Active dendrites, potassium channels and synaptic plasticity.
2003,
Pubmed
Kim,
Three-dimensional structure of I(to); Kv4.2-KChIP2 ion channels by electron microscopy at 21 Angstrom resolution.
2004,
Pubmed
Kim,
Kv4 potassium channel subunits control action potential repolarization and frequency-dependent broadening in rat hippocampal CA1 pyramidal neurones.
2005,
Pubmed
Kreusch,
Crystal structure of the tetramerization domain of the Shaker potassium channel.
1998,
Pubmed
Kunjilwar,
KChIP3 rescues the functional expression of Shal channel tetramerization mutants.
2004,
Pubmed
Kuo,
A defect in the Kv channel-interacting protein 2 (KChIP2) gene leads to a complete loss of I(to) and confers susceptibility to ventricular tachycardia.
2001,
Pubmed
Li,
Assembly of potassium channels.
1993,
Pubmed
Liang,
Structural Insights into KChIP4a Modulation of Kv4.3 Inactivation.
2009,
Pubmed
,
Xenbase
Morohashi,
Molecular cloning and characterization of CALP/KChIP4, a novel EF-hand protein interacting with presenilin 2 and voltage-gated potassium channel subunit Kv4.
2002,
Pubmed
Nadal,
Evidence for the presence of a novel Kv4-mediated A-type K(+) channel-modifying factor.
2001,
Pubmed
,
Xenbase
Nagaya,
Potassium channel alpha and beta subunits assemble in the endoplasmic reticulum.
1997,
Pubmed
Pioletti,
Three-dimensional structure of the KChIP1-Kv4.3 T1 complex reveals a cross-shaped octamer.
2006,
Pubmed
,
Xenbase
Scannevin,
Two N-terminal domains of Kv4 K(+) channels regulate binding to and modulation by KChIP1.
2004,
Pubmed
Schwenk,
NMR analysis of KChIP4a reveals structural basis for control of surface expression of Kv4 channel complexes.
2008,
Pubmed
Sheng,
Subcellular segregation of two A-type K+ channel proteins in rat central neurons.
1992,
Pubmed
,
Xenbase
Sheng,
Contrasting subcellular localization of the Kv1.2 K+ channel subunit in different neurons of rat brain.
1994,
Pubmed
Shibata,
A-type K+ current mediated by the Kv4 channel regulates the generation of action potential in developing cerebellar granule cells.
2000,
Pubmed
Shibata,
A fundamental role for KChIPs in determining the molecular properties and trafficking of Kv4.2 potassium channels.
2003,
Pubmed
Song,
Somatodendritic depolarization-activated potassium currents in rat neostriatal cholinergic interneurons are predominantly of the A type and attributable to coexpression of Kv4.2 and Kv4.1 subunits.
1998,
Pubmed
Strang,
The role of Zn2+ in Shal voltage-gated potassium channel formation.
2003,
Pubmed
Wang,
Functionally active t1-t1 interfaces revealed by the accessibility of intracellular thiolate groups in kv4 channels.
2005,
Pubmed
,
Xenbase
Wang,
Voltage-dependent gating rearrangements in the intracellular T1-T1 interface of a K+ channel.
2006,
Pubmed
,
Xenbase
Wang,
Structural basis for modulation of Kv4 K+ channels by auxiliary KChIP subunits.
2007,
Pubmed
,
Xenbase
Wang,
Zn2+-dependent redox switch in the intracellular T1-T1 interface of a Kv channel.
2007,
Pubmed
,
Xenbase
Xiong,
Differential distribution of KChIPs mRNAs in adult mouse brain.
2004,
Pubmed
Xu,
Assembly of voltage-gated potassium channels. Conserved hydrophilic motifs determine subfamily-specific interactions between the alpha-subunits.
1995,
Pubmed
Yi,
Controlling potassium channel activities: Interplay between the membrane and intracellular factors.
2001,
Pubmed
Zerangue,
A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels.
1999,
Pubmed
,
Xenbase
Zhou,
Structural insights into the functional interaction of KChIP1 with Shal-type K(+) channels.
2004,
Pubmed
