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doi:10.1534/genetics.105.043174
A more recent version of this article appeared on August 1, 2005.
REGULAR RESEARCH PAPERS |
The mei-P26 gene encodes an RBCC-NHL protein that regulates seizure susceptibility in Drosophila
Albert E Glasscock 1*, Ayush Singhania 1 and Mark A Tanouye 1
1 University of California, Berkeley
* To whom correspondence should be addressed. E-mail: edwardg76{at}yahoo.com.
Submitted on March 10, 2005
Revised on April 14, 2005
Accepted on 21 April 2005
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 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.
Key Words: RBCC-NHL protein, bang-sensitive, epilepsy, mei-P26, seizure
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