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
2010 Mar 23;10712:5617-21. doi: 10.1073/pnas.1001494107.
Show Gene links
Show Anatomy links
A Drosophila behavioral mutant, down and out (dao), is defective in an essential regulator of Erg potassium channels.
Fergestad T
,
Sale H
,
Bostwick B
,
Schaffer A
,
Ho L
,
Robertson GA
,
Ganetzky B
.
???displayArticle.abstract???
To signal properly, excitable cells must establish and maintain the correct balance of various types of ion channels that increase or decrease membrane excitability. The mechanisms by which this balance is regulated remain largely unknown. Here, we describe a regulatory mechanism uncovered by a Drosophila behavioral mutant, down and out (dao). At elevated temperatures, dao loss-of-function mutants exhibit seizures associated with spontaneous bursts of neural activity. This phenotype closely resembles that of seizure mutations, which impair activity of ether-a-go-go-related gene (Erg)-type potassium channels. Conversely, neural over-expression of wild-type Dao confers dominant temperature-sensitive paralysis with kinetics reminiscent of paralytic sodium-channel mutants. The over-expression phenotype of dao is suppressed in a seizure mutant background, suggesting that Dao acts by an effect on Erg channels. In support of this hypothesis, functional expression of Erg channels in a heterologous system is dependent on the presence of Dao. These results indicate that Dao has an important role in establishing the proper level of neuronal membrane excitability by regulating functional expression of Erg channels.
Anderson,
Most LQT2 mutations reduce Kv11.1 (hERG) current by a class 2 (trafficking-deficient) mechanism.
2006, Pubmed
Anderson,
Most LQT2 mutations reduce Kv11.1 (hERG) current by a class 2 (trafficking-deficient) mechanism.
2006,
Pubmed
Atkinson,
A component of calcium-activated potassium channels encoded by the Drosophila slo locus.
1991,
Pubmed
Blatch,
The tetratricopeptide repeat: a structural motif mediating protein-protein interactions.
1999,
Pubmed
Brand,
Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.
1993,
Pubmed
Chang,
The nonsense-mediated decay RNA surveillance pathway.
2007,
Pubmed
Curran,
A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome.
1995,
Pubmed
Elkins,
Conduction in the giant nerve fiber pathway in temperature-sensitive paralytic mutants of Drosophila.
1990,
Pubmed
Feinstein,
Identification of homeotic target genes in Drosophila melanogaster including nervy, a proto-oncogene homologue.
1995,
Pubmed
Feng,
Cloning and functional analysis of TipE, a novel membrane protein that enhances Drosophila para sodium channel function.
1995,
Pubmed
,
Xenbase
Fergestad,
Metabolic disruption in Drosophila bang-sensitive seizure mutants.
2006,
Pubmed
Ficker,
Novel characteristics of a misprocessed mutant HERG channel linked to hereditary long QT syndrome.
2000,
Pubmed
,
Xenbase
Furutani,
Novel mechanism associated with an inherited cardiac arrhythmia: defective protein trafficking by the mutant HERG (G601S) potassium channel.
1999,
Pubmed
,
Xenbase
Ganetzky,
Neurogenetic analysis of Drosophila mutations affecting sodium channels: synergistic effects on viability and nerve conduction in double mutants involving tip-E.
1986,
Pubmed
Gross,
DEAF-1, a novel protein that binds an essential region in a Deformed response element.
1996,
Pubmed
Hanrahan,
RNA editing of the Drosophila para Na(+) channel transcript. Evolutionary conservation and developmental regulation.
2000,
Pubmed
Jackson,
Genetic modifications of voltage-sensitive sodium channels in Drosophila: gene dosage studies of the seizure locus.
1985,
Pubmed
Jackson,
The tip-E mutation of Drosophila decreases saxitoxin binding and interacts with other mutations affecting nerve membrane excitability.
1986,
Pubmed
Jackson,
Two types of mutants affecting voltage-sensitive sodium channels in Drosophila melanogaster.
,
Pubmed
Kuebler,
Modifications of seizure susceptibility in Drosophila.
2000,
Pubmed
Lamb,
Tetratrico peptide repeat interactions: to TPR or not to TPR?
1995,
Pubmed
Lee,
Electroconvulsive seizure behavior in Drosophila: analysis of the physiological repertoire underlying a stereotyped action pattern in bang-sensitive mutants.
2002,
Pubmed
Loughney,
Molecular analysis of the para locus, a sodium channel gene in Drosophila.
1989,
Pubmed
Oh,
A P-element insertion screen identified mutations in 455 novel essential genes in Drosophila.
2003,
Pubmed
Rajamani,
Pharmacological rescue of human K(+) channel long-QT2 mutations: human ether-a-go-go-related gene rescue without block.
2002,
Pubmed
Robertson,
A stable genomic source of P element transposase in Drosophila melanogaster.
1988,
Pubmed
Sanguinetti,
A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel.
1995,
Pubmed
,
Xenbase
Seeburg,
RNA helicase participates in the editing game.
2000,
Pubmed
Stern,
Dosage effects of a Drosophila sodium channel gene on behavior and axonal excitability.
1990,
Pubmed
Titus,
The Drosophila erg K+ channel polypeptide is encoded by the seizure locus.
1997,
Pubmed
Trudeau,
HERG, a human inward rectifier in the voltage-gated potassium channel family.
1995,
Pubmed
Walker,
Co-chaperone FKBP38 promotes HERG trafficking.
2007,
Pubmed
Wang,
The seizure locus encodes the Drosophila homolog of the HERG potassium channel.
1997,
Pubmed
Warmke,
Functional expression of Drosophila para sodium channels. Modulation by the membrane protein TipE and toxin pharmacology.
1997,
Pubmed
,
Xenbase
Zhou,
Correction of defective protein trafficking of a mutant HERG potassium channel in human long QT syndrome. Pharmacological and temperature effects.
1999,
Pubmed
