The mei-P26 gene encodes a RING finger B-box coiled-coil-NHL protein that regulates seizure susceptibility in Drosophilia
The mei-P26 gene encodes a RING finger B-box coiled-coil-NHL protein that regulates seizure susceptibility in Drosophilia
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DOI：
10.1534/genetics.105.043174
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发表时间：
2005-08-01
期刊：
影响因子：
3.3
通讯作者：
Tanouye, MA
中科院分区：
文献类型：
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作者：
Glasscock, E;Singhania, A;Tanouye, MA
癫痫抑制突变提供了独特的见解基因和机制参与调节神经系统兴奋性。果蝇bang-sensitive （BS）突变体是鉴定癫痫抑制因子的有用工具，因为它们是一种具有良好特征的癫痫模型。在这里，我们描述了一种新的果蝇癫痫抑制突变体的分离和特征，该突变体是由减数分裂基因mei-P26的破坏引起的，该基因属于rbc - nhl蛋白家族。mei-P26突变减少了机械刺激和电休克后易休克（eas）和痉挛（sda）癫痫苍蝇的癫痫发作。此外，突变型mei-P26果蝇的癫痫发作阈值至少是野生型的三倍。mei-P26的表型似乎是由NHL蛋白-蛋白相互作用域的一个关键残基的错义突变引起的。这些结果揭示了mei-P26在种系外作为癫痫易感性调节剂的令人惊讶的作用，可能是通过作为泛素连接酶影响突触发育。
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 clectroconvulsive 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.