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.
Neurochem Res
2008 Oct 01;3310:2078-84. doi: 10.1007/s11064-008-9688-7.
Show Gene links
Show Anatomy links
Enhanced trafficking of tetrameric Kv4.3 channels by KChIP1 clamping.
Cui YY
,
Liang P
,
Wang KW
.
???displayArticle.abstract???
The cytoplamsic auxiliary KChIPs modulate surface expression and gating properties of Kv4 channels. Recent co-crystal structure of Kv4.3 N-terminus and KChIP1 reveals a clamping action of the complex in which a single KChIP1 molecule laterally binds two neighboring Kv4.3 N-termini at different locations, thus forming two contact interfaces involved in the protein-protein interaction. In the second interface, it functions to stabilize the tetrameric assembly, but the role it plays in channel trafficking remains elusive. In this study, we examined the effects of KChIP1 on Kv4 protein trafficking in COS-7 cells expressing EGFP-tagged Kv4.3 channels using confocal microscopy. Mutations either in KChIP1 (KChIP1 L39E-Y57A-K61A) or Kv4.3 (Kv4.3 E70A-F73E) that disrupt the protein-protein interaction within the second interface can reduce surface expression of Kv4 channel proteins. Kv4.3 C110A, the Zn2+ binding site mutation in T1 domain, that disrupts the tetrameric assembly of the channels can be rescued by WT KChIP1, but not the KChIP1 triple mutant. These results were further confirmed by whole cell current recordings in oocytes. Our findings show that key residues of second interface involved in stabilizing tetrameric assembly can regulate the channel trafficking, indicating an intrinsic link between tetrameric assembly and channel trafficking. The results also suggest that formation of octameric Kv4 and KChIP complex by KChIPs clamping takes place before their trafficking to final destination on the cell surface.
Abbott,
A superfamily of small potassium channel subunits: form and function of the MinK-related peptides (MiRPs).
1998, Pubmed
Abbott,
A superfamily of small potassium channel subunits: form and function of the MinK-related peptides (MiRPs).
1998,
Pubmed
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
Callsen,
Contribution of N- and C-terminal Kv4.2 channel domains to KChIP interaction [corrected].
2005,
Pubmed
Holmqvist,
Elimination of fast inactivation in Kv4 A-type potassium channels by an auxiliary subunit domain.
2002,
Pubmed
,
Xenbase
Jahng,
Zinc mediates assembly of the T1 domain of the voltage-gated K channel 4.2.
2002,
Pubmed
Jow,
Functional coupling of intracellular calcium and inactivation of voltage-gated Kv1.1/Kvbeta1.1 A-type K+ channels.
2004,
Pubmed
,
Xenbase
Kim,
Three-dimensional structure of I(to); Kv4.2-KChIP2 ion channels by electron microscopy at 21 Angstrom resolution.
2004,
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,
Specification of subunit assembly by the hydrophilic amino-terminal domain of the Shaker potassium channel.
1992,
Pubmed
Long,
Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
2005,
Pubmed
Nadal,
Evidence for the presence of a novel Kv4-mediated A-type K(+) channel-modifying factor.
2001,
Pubmed
,
Xenbase
Pioletti,
Three-dimensional structure of the KChIP1-Kv4.3 T1 complex reveals a cross-shaped octamer.
2006,
Pubmed
,
Xenbase
Rhodes,
KChIPs and Kv4 alpha subunits as integral components of A-type potassium channels in mammalian brain.
2004,
Pubmed
Scannevin,
Two N-terminal domains of Kv4 K(+) channels regulate binding to and modulation by KChIP1.
2004,
Pubmed
Shibata,
A fundamental role for KChIPs in determining the molecular properties and trafficking of Kv4.2 potassium channels.
2003,
Pubmed
Wang,
Structural basis for modulation of Kv4 K+ channels by auxiliary KChIP subunits.
2007,
Pubmed
,
Xenbase
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
