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.
J Biol Chem
2012 Dec 21;28752:43972-83. doi: 10.1074/jbc.M112.388033.
Show Gene links
Show Anatomy links
Functional analysis of missense mutations in Kv8.2 causing cone dystrophy with supernormal rod electroretinogram.
Smith KE
,
Wilkie SE
,
Tebbs-Warner JT
,
Jarvis BJ
,
Gallasch L
,
Stocker M
,
Hunt DM
.
???displayArticle.abstract???
Mutations in KCNV2 have been proposed as the molecular basis for cone dystrophy with supernormal rod electroretinogram. KCNV2 codes for the modulatory voltage-gated potassium channel α-subunit, Kv8.2, which is incapable of forming functional channels on its own. Functional heteromeric channels are however formed with Kv2.1 in heterologous expression systems, with both α-subunit genes expressed in rod and cone photoreceptors. Of the 30 mutations identified in the KCNV2 gene, we have selected three missense mutations localized in the potassium channel pore and two missense mutations localized in the tetramerization domain for analysis. We characterized the differences between homomeric Kv2.1 and heteromeric Kv2.1/Kv8.2 channels and investigated the influence of the selected mutations on the function of heteromeric channels. We found that two pore mutations (W467G and G478R) led to the formation of nonconducting heteromeric Kv2.1/Kv8.2 channels, whereas the mutations localized in the tetramerization domain prevented heteromer generation and resulted in the formation of homomeric Kv2.1 channels only. Consequently, our study suggests the existence of two distinct molecular mechanisms involved in the disease pathology.
Beech,
Characterization of a voltage-gated K+ channel that accelerates the rod response to dim light.
1989, Pubmed
Beech,
Characterization of a voltage-gated K+ channel that accelerates the rod response to dim light.
1989,
Pubmed
Ben Salah,
Novel KCNV2 mutations in cone dystrophy with supernormal rod electroretinogram.
2008,
Pubmed
Bixby,
Zn2+-binding and molecular determinants of tetramerization in voltage-gated K+ channels.
1999,
Pubmed
Bocksteins,
Conserved negative charges in the N-terminal tetramerization domain mediate efficient assembly of Kv2.1 and Kv2.1/Kv6.4 channels.
2009,
Pubmed
Bocksteins,
Electrically silent Kv subunits: their molecular and functional characteristics.
2012,
Pubmed
Castellano,
Identification and functional characterization of a K+ channel alpha-subunit with regulatory properties specific to brain.
1997,
Pubmed
Chang,
The nonsense-mediated decay RNA surveillance pathway.
2007,
Pubmed
Chiara,
A small domain in the N terminus of the regulatory alpha-subunit Kv2. 3 modulates Kv2.1 potassium channel gating.
1999,
Pubmed
Christie,
Heteropolymeric potassium channels expressed in Xenopus oocytes from cloned subunits.
1990,
Pubmed
,
Xenbase
Cia,
Voltage-gated channels and calcium homeostasis in mammalian rod photoreceptors.
2005,
Pubmed
Czirják,
Characterization of the heteromeric potassium channel formed by kv2.1 and the retinal subunit kv8.2 in Xenopus oocytes.
2007,
Pubmed
,
Xenbase
Demontis,
Properties and functional roles of hyperpolarization-gated currents in guinea-pig retinal rods.
1999,
Pubmed
Es-Salah-Lamoureux,
Blockade of permeation by potassium but normal gating of the G628S nonconducting hERG channel mutant.
2011,
Pubmed
,
Xenbase
Frings,
Characterization of ether-à-go-go channels present in photoreceptors reveals similarity to IKx, a K+ current in rod inner segments.
1998,
Pubmed
Gouras,
Cone dystrophy, nyctalopia, and supernormal rod responses. A new retinal degeneration.
1983,
Pubmed
Gutman,
International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels.
2005,
Pubmed
Hejtmancik,
Mutations in KCNJ13 cause autosomal-dominant snowflake vitreoretinal degeneration.
2008,
Pubmed
Horton,
Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extension.
1989,
Pubmed
Hugnot,
Kv8.1, a new neuronal potassium channel subunit with specific inhibitory properties towards Shab and Shaw channels.
1996,
Pubmed
,
Xenbase
Isacoff,
Evidence for the formation of heteromultimeric potassium channels in Xenopus oocytes.
1990,
Pubmed
,
Xenbase
Jentsch,
Ion channels: function unravelled by dysfunction.
2004,
Pubmed
Kerschensteiner,
Heteromeric assembly of Kv2.1 with Kv9.3: effect on the state dependence of inactivation.
1999,
Pubmed
,
Xenbase
Kerschensteiner,
Fluorescence measurements reveal stoichiometry of K+ channels formed by modulatory and delayed rectifier alpha-subunits.
2005,
Pubmed
Khan,
'Cone dystrophy with supranormal rod response' in children.
2012,
Pubmed
Klemic,
Inactivation of Kv2.1 potassium channels.
1998,
Pubmed
,
Xenbase
Kramer,
Modulation of potassium channel gating by coexpression of Kv2.1 with regulatory Kv5.1 or Kv6.1 alpha-subunits.
1998,
Pubmed
,
Xenbase
Kullmann,
Neurological channelopathies.
2010,
Pubmed
Lee,
Structural determinant for assembly of mammalian K+ channels.
1994,
Pubmed
,
Xenbase
Li,
Specification of subunit assembly by the hydrophilic amino-terminal domain of the Shaker potassium channel.
1992,
Pubmed
Littink,
Homozygosity mapping in patients with cone-rod dystrophy: novel mutations and clinical characterizations.
2010,
Pubmed
Mederos Y Schnitzler,
Mutation of histidine 105 in the T1 domain of the potassium channel Kv2.1 disrupts heteromerization with Kv6.3 and Kv6.4.
2009,
Pubmed
Ottschytsch,
Obligatory heterotetramerization of three previously uncharacterized Kv channel alpha-subunits identified in the human genome.
2002,
Pubmed
Park,
Graded regulation of the Kv2.1 potassium channel by variable phosphorylation.
2006,
Pubmed
Park,
Proteomic analyses of K(v)2.1 channel phosphorylation sites determining cell background specific differences in function.
2007,
Pubmed
Patel,
Kv2.1/Kv9.3, an ATP-dependent delayed-rectifier K+ channel in pulmonary artery myocytes.
1999,
Pubmed
,
Xenbase
Post,
Kv2.1 and electrically silent Kv6.1 potassium channel subunits combine and express a novel current.
1996,
Pubmed
,
Xenbase
Ramu,
Enzymatic activation of voltage-gated potassium channels.
2006,
Pubmed
Robson,
"Cone dystrophy with supernormal rod electroretinogram": a comprehensive genotype/phenotype study including fundus autofluorescence and extensive electrophysiology.
2010,
Pubmed
Ruppersberg,
Heteromultimeric channels formed by rat brain potassium-channel proteins.
1990,
Pubmed
,
Xenbase
Salinas,
Modes of regulation of shab K+ channel activity by the Kv8.1 subunit.
1997,
Pubmed
,
Xenbase
Salinas,
New modulatory alpha subunits for mammalian Shab K+ channels.
1997,
Pubmed
Schneider,
NIH Image to ImageJ: 25 years of image analysis.
2012,
Pubmed
Schwake,
Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy.
2000,
Pubmed
,
Xenbase
Sergouniotis,
High-resolution optical coherence tomography imaging in KCNV2 retinopathy.
2012,
Pubmed
Shen,
Molecular recognition and assembly sequences involved in the subfamily-specific assembly of voltage-gated K+ channel subunit proteins.
1995,
Pubmed
Stocker,
Subunit assembly and domain analysis of electrically silent K+ channel alpha-subunits of the rat Kv9 subfamily.
1999,
Pubmed
,
Xenbase
Thiagalingam,
Novel mutations in the KCNV2 gene in patients with cone dystrophy and a supernormal rod electroretinogram.
2007,
Pubmed
Tu,
Voltage-gated K+ channels contain multiple intersubunit association sites.
1996,
Pubmed
,
Xenbase
VanDongen,
Alteration and restoration of K+ channel function by deletions at the N- and C-termini.
1990,
Pubmed
Werblin,
Time- and voltage-dependent ionic components of the rod response.
1979,
Pubmed
Wissinger,
Large deletions of the KCNV2 gene are common in patients with cone dystrophy with supernormal rod response.
2011,
Pubmed
Wissinger,
Cone dystrophy with supernormal rod response is strictly associated with mutations in KCNV2.
2008,
Pubmed
Wu,
Mutations in the gene KCNV2 encoding a voltage-gated potassium channel subunit cause "cone dystrophy with supernormal rod electroretinogram" in humans.
2006,
Pubmed
Xu,
Removal of phospho-head groups of membrane lipids immobilizes voltage sensors of K+ channels.
2008,
Pubmed
,
Xenbase
Yagi,
Ionic conductances of monkey solitary cone inner segments.
1994,
Pubmed
Yellen,
The voltage-gated potassium channels and their relatives.
2002,
Pubmed
Zerangue,
An artificial tetramerization domain restores efficient assembly of functional Shaker channels lacking T1.
2000,
Pubmed
,
Xenbase
Zhu,
Structural and functional characterization of Kv6.2 a new gamma-subunit of voltage-gated potassium channel.
1999,
Pubmed
