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.
RNA editing generates tissue-specific sodium channels with distinct gating properties.
Song W
,
Liu Z
,
Tan J
,
Nomura Y
,
Dong K
.
???displayArticle.abstract???
Sodium channels play an essential role in generating the action potential in eukaryotic cells, and their transcripts, especially those in insects, undergo extensive A-to-I RNA editing. The functional consequences of RNA editing of sodium channel transcripts, however, have yet to be determined. We characterized 20 splice variants of the German cockroach sodium channel gene BgNa(v). Functional analysis revealed that these variants exhibited a broad range of voltage-dependent activation and inactivation. Further analysis of two variants, BgNa(v)1-1 and BgNa(v)1-2, which activate at more depolarizing membrane potentials than other variants, showed that RNA editing events were responsible for variant-specific gating properties. Two U-to-C editing sites identified in BgNa(v)1-1 resulted in a Leu to Pro change in segment 1 of domain III (IIIS1) and a Val to Ala change in IVS4. The Leu to Pro change shifted both the voltage dependence of activation and steady-state inactivation in the depolarizing direction. Two A-to-I editing events in BgNa(v)1-2 resulted in a Lys to Arg change in IS2 and an Ile to Met change in IVS3. The Lys to Arg change shifted the voltage dependence of activation in the depolarizing direction. Moreover, these RNA editing events occurred in a tissue-specific and development-specific manner. Our findings provide direct evidence that RNA editing is an important mechanism generating tissue-/cell type-specific functional variants of sodium channels.
Burns,
Regulation of serotonin-2C receptor G-protein coupling by RNA editing.
1997, Pubmed
Burns,
Regulation of serotonin-2C receptor G-protein coupling by RNA editing.
1997,
Pubmed
Byerly,
Ionic currents of Drosophila neurons in embryonic cultures.
1988,
Pubmed
Catterall,
From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels.
2000,
Pubmed
Catterall,
International Union of Pharmacology. XXXIX. Compendium of voltage-gated ion channels: sodium channels.
2003,
Pubmed
Crill,
Persistent sodium current in mammalian central neurons.
1996,
Pubmed
Dib-Hajj,
NaN/Nav1.9: a sodium channel with unique properties.
2002,
Pubmed
Dietrich,
Functional analysis of a voltage-gated sodium channel and its splice variant from rat dorsal root ganglia.
1998,
Pubmed
,
Xenbase
Dong,
A single amino acid change in the para sodium channel protein is associated with knockdown-resistance (kdr) to pyrethroid insecticides in German cockroach.
1997,
Pubmed
Feng,
Cloning and functional analysis of TipE, a novel membrane protein that enhances Drosophila para sodium channel function.
1995,
Pubmed
,
Xenbase
Goldin,
Resurgence of sodium channel research.
2001,
Pubmed
Goldin,
Nomenclature of voltage-gated sodium channels.
2000,
Pubmed
Grauso,
Novel putative nicotinic acetylcholine receptor subunit genes, Dalpha5, Dalpha6 and Dalpha7, in Drosophila melanogaster identify a new and highly conserved target of adenosine deaminase acting on RNA-mediated A-to-I pre-mRNA editing.
2002,
Pubmed
Gustafson,
Mutually exclusive exon splicing of type III brain sodium channel alpha subunit RNA generates developmentally regulated isoforms in rat brain.
1993,
Pubmed
Hanrahan,
RNA editing of the Drosophila para Na(+) channel transcript. Evolutionary conservation and developmental regulation.
2000,
Pubmed
Lee,
Developmental regulation of alternative exon usage in the house fly Vssc1 sodium channel gene.
2002,
Pubmed
Lomeli,
Control of kinetic properties of AMPA receptor channels by nuclear RNA editing.
1994,
Pubmed
,
Xenbase
Loughney,
Molecular analysis of the para locus, a sodium channel gene in Drosophila.
1989,
Pubmed
Nagalla,
Cloning of complementary DNAs encoding the amphibian bombesin-like peptides Phe8 and Leu8 phyllolitorin from Phyllomedusa sauvagei: potential role of U to C RNA editing in generating neuropeptide diversity.
1994,
Pubmed
Niswender,
RNA editing of the human serotonin 5-hydroxytryptamine 2C receptor silences constitutive activity.
1999,
Pubmed
Numann,
Functional modulation of brain sodium channels by protein kinase C phosphorylation.
1991,
Pubmed
O'Dowd,
Sodium current density correlates with expression of specific alternatively spliced sodium channel mRNAs in single neurons.
1995,
Pubmed
Palladino,
A-to-I pre-mRNA editing in Drosophila is primarily involved in adult nervous system function and integrity.
2000,
Pubmed
Patton,
RNA editing generates a diverse array of transcripts encoding squid Kv2 K+ channels with altered functional properties.
1997,
Pubmed
Plummer,
Alternative splicing of the sodium channel SCN8A predicts a truncated two-domain protein in fetal brain and non-neuronal cells.
1997,
Pubmed
Reenan,
The mle(napts) RNA helicase mutation in drosophila results in a splicing catastrophe of the para Na+ channel transcript in a region of RNA editing.
2000,
Pubmed
Rosenthal,
Extensive editing of mRNAs for the squid delayed rectifier K+ channel regulates subunit tetramerization.
2002,
Pubmed
,
Xenbase
Sarao,
Developmentally regulated alternative RNA splicing of rat brain sodium channel mRNAs.
1991,
Pubmed
Schaller,
Alternatively spliced sodium channel transcripts in brain and muscle.
1992,
Pubmed
Seeburg,
A-to-I editing: new and old sites, functions and speculations.
2002,
Pubmed
Seeburg,
RNA helicase participates in the editing game.
2000,
Pubmed
Seeburg,
RNA editing of brain glutamate receptor channels: mechanism and physiology.
1998,
Pubmed
Semenov,
Diversification of Drosophila chloride channel gene by multiple posttranscriptional mRNA modifications.
1999,
Pubmed
Sharma,
RNA editing in the Wilms' tumor susceptibility gene, WT1.
1994,
Pubmed
Smith,
RNA editing in the Drosophila DMCA1A calcium-channel alpha 1 subunit transcript.
1998,
Pubmed
Smith,
Phosphorylation of brain sodium channels in the I--II linker modulates channel function in Xenopus oocytes.
1996,
Pubmed
,
Xenbase
Smith,
Phosphorylation at a single site in the rat brain sodium channel is necessary and sufficient for current reduction by protein kinase A.
1997,
Pubmed
,
Xenbase
Smith,
The L1014F point mutation in the house fly Vssc1 sodium channel confers knockdown resistance to pyrethroids.
1997,
Pubmed
,
Xenbase
Smith,
Potentiation of rat brain sodium channel currents by PKA in Xenopus oocytes involves the I-II linker.
2000,
Pubmed
,
Xenbase
Sommer,
RNA editing in brain controls a determinant of ion flow in glutamate-gated channels.
1991,
Pubmed
Tan,
Novel sodium channel gene mutations in Blattella germanica reduce the sensitivity of expressed channels to deltamethrin.
2002,
Pubmed
,
Xenbase
Tan,
Alternative splicing of an insect sodium channel gene generates pharmacologically distinct sodium channels.
2002,
Pubmed
,
Xenbase
Thackeray,
Conserved alternative splicing patterns and splicing signals in the Drosophila sodium channel gene para.
1995,
Pubmed
Thackeray,
Developmentally regulated alternative splicing generates a complex array of Drosophila para sodium channel isoforms.
1994,
Pubmed
Villegas,
A putative RNA editing from U to C in a mouse mitochondrial transcript.
2002,
Pubmed
Warmke,
Functional expression of Drosophila para sodium channels. Modulation by the membrane protein TipE and toxin pharmacology.
1997,
Pubmed
,
Xenbase
West,
A phosphorylation site in the Na+ channel required for modulation by protein kinase C.
1991,
Pubmed
Yu,
Overview of the voltage-gated sodium channel family.
2003,
Pubmed
