The mei-P26 gene encodes a RING finger B-box coiled-coil-NHL protein that regulates seizure susceptibility in Drosophilia.
Seizure-suppressor mutations provide unique insight into the genes and mechanisms involved in regulating nervous system excitability. Drosophila bang-sensitive (BS) mutants present a useful tool for identifying seizure suppressors since they are a well-characterized epilepsy model. Here we describe the isolation and characterization of a new Drosophila seizure-suppressor mutant that results from disruption of the meiotic gene mei-P26, which belongs to the RBCC-NHL family of proteins. The mei-P26 mutation reduces seizures in easily shocked (eas) and slamdance (sda) epileptic flies following mechanical stimulation and electroconvulsive shock. In addition, mutant mei-P26 flies exhibit seizure thresholds at least threefold greater than those of wild type. The mei-P26 phenotypes appear to result from missense mutation of a critical residue in the NHL protein-protein interaction domain of the protein. These results reveal a surprising role for mei-P26 outside of the germline as a regulator of seizure susceptibility, possibly by affecting synaptic development as a ubiquitin ligase.
Glasscock
Edward
E
Department of Molecular and Cell Biology, Division of Neurobiology, University of California, Berkeley, CA 94720, USA. edwardg@uclink.berkeley.edu
Singhania
Ayush
A
Tanouye
Mark A
MA
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002874:Chromosome Mapping; D002875:Chromosomes; D017124:Conserved Sequence; D004198:Disease Susceptibility; D004330:Drosophila / Q000235:genetics* / Q000502:physiology; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology*; D004597:Electroshock; D005786:Gene Expression Regulation; D017344:Genes, Insect; D008540:Meiosis; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D017434:Protein Structure, Tertiary; D012640:Seizures / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013489:Suppression, Genetic
D029721:Drosophila Proteins