The seizure locus encodes the Drosophila homolog of the HERG potassium channel.
Mutations in the seizure (sei) locus cause temperature-induced hyperactivity, followed by paralysis. Gene cloning studies have established that the seizure gene product is the Drosophila homolog of HERG, a member of the eag family of K+ channels implicated in one form of hereditary long QT syndrome in humans. A series of five null alleles with premature stop codons are all recessive, but viable. A missense mutation in the sei gene, which changes the charge at a conserved glutamate residue near the outer mouth of the pore, has a semidominant phenotype, suggesting that the mutant seizure protein acts as a poison in a multimeric complex. Transformation rescue of a null allele with a cDNA under the control of an inducible promoter demonstrates that induced expression of seizure potassium channels in adults rescues the paralytic phenotype. This rescue decays with a t1/2 of approximately 1-1.5 d after gene induction is discontinued, providing the first estimate of ion channel stability in an intact, multicellular animal.
Wang
X J
XJ
Department of Biochemical Pharmacology, State University of New York at Buffalo 14260-1200, USA.
Reynolds
E R
ER
Déak
P
P
Hall
L M
LM
D000595:Amino Acid Sequence; D000818:Animals; D027682:Cation Transport Proteins; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D005786:Gene Expression Regulation; D006801:Humans; D006948:Hyperkinesis / Q000235:genetics; D008133:Long QT Syndrome / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010243:Paralysis / Q000235:genetics; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D017434:Protein Structure, Tertiary; D017422:Sequence Analysis, DNA; D015534:Trans-Activators; D015533:Transcriptional Activation; D000071230:Transcriptional Regulator ERG
D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; C496883:eag protein, Drosophila