In vivo analysis of a gain-of-function mutation in the Drosophila eag-encoded K⁺ channel

Neuronal Na⁺ and K⁺ channels elicit currents in opposing directions and thus have opposing effects on neuronal excitability. Mutations in genes encoding Na⁺ or K⁺ channels often interact genetically, leading either to phenotypic suppression or enhancement for genes with opposing or similar effects on excitability respectively. For example, the effects of mutations in Shaker (Sh), which encodes a K⁺ channel subunit, are suppressed by loss of function mutations in the Na⁺ channel structural gene para, but enhanced by loss of function mutations in a second K⁺ channel encoded by eag. Here we identify two novel mutations that suppress the effects of a Sh mutation on behavior and neuronal excitability. We used recombination mapping to localize both mutations to the eag locus, and we used sequence analysis to determine that both mutations are caused by a single amino acid substitution (G297E) in the S2-S3 linker of Eag. Because these novel eag mutations confer opposite phenotypes to eag loss of function mutations, we suggest that eag^G297E causes an eag gain of function phenotype. We hypothesize that the G297E substitution may cause premature, prolonged or constitutive opening of the Eag channel by favoring the "unlocked" state of the channel.

Key Words: behavioral, electrophysiology, excitability, mutant, neuronal

Online ISS 1091-6490
Copyright 2008 by the Genetics Society of America
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