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Originally published as Genetics Published Articles Ahead of Print on June 3, 2005.

Genetics, Vol. 170, 1677-1689, August 2005, Copyright © 2005
doi:10.1534/genetics.105.043174

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The mei-P26 Gene Encodes a RING Finger B-box Coiled-Coil-NHL Protein That Regulates Seizure Susceptibility in Drosophilia

Edward Glasscock*,1, Ayush Singhania* and Mark A. Tanouye*,{dagger}

* Department of Molecular and Cell Biology, Division of Neurobiology
{dagger} Department of Environmental Science, Policy and Management, Division of Insect Biology, University of California, Berkeley, California 94720

1 Corresponding author: Department of Molecular and Cell Biology, Life Sciences Addition, Room 131, University of California, Berkeley, CA 94720.
E-mail: edwardg{at}uclink.berkeley.edu

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.




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