Siddiqui Salma Z, Brown David D R, Accardi Michael V, Forrester Sean G
Applied Bioscience Graduate Program, University of Ontario Institute of Technology, Oshawa, Ontario, Canada.
Mol Biochem Parasitol. 2012 Oct;185(2):137-44. doi: 10.1016/j.molbiopara.2012.08.004. Epub 2012 Aug 23.
We have identified and characterized a novel cys-loop GABA receptor subunit (Hco-LGC-38) from the parasitic nematode Haemonchus contortus. This subunit is present in parasitic and free-living nematodes and shares similarity to both the UNC-49 group of GABA receptor subunits from nematodes and the resistant to dieldrin (RDL) receptors of insects. Expression of the Hco-lgc-38 gene in Xenopus oocytes and subsequent electrophysiological analysis has revealed that the gene encodes a homomeric channel sensitive to GABA (EC(50) 19 μM) and the GABA analogue muscimol. The sensitivity of the Hco-LGC-38 channel to GABA is similar to reported values for the Drosophila RDL receptor whereas its lower sensitivity to muscimol is similar to nematode GABA receptors. Hco-LGC-38 is also highly sensitive to the channel blocker picrotoxin and moderately sensitive to fipronil and dieldrin. Homology modeling of Hco-LGC-38 and subsequent docking of GABA and muscimol into the binding site has uncovered several types of potential interactions with binding-site residues and overall appears to share similarity with models of other invertebrate GABA receptors.
我们已经从寄生线虫捻转血矛线虫中鉴定并表征了一种新型的cys-loop GABA受体亚基（Hco-LGC-38）。该亚基存在于寄生和自由生活的线虫中，与线虫的UNC-49组GABA受体亚基以及昆虫的抗狄氏剂（RDL）受体具有相似性。Hco-lgc-38基因在非洲爪蟾卵母细胞中的表达及随后的电生理分析表明，该基因编码一个对GABA（EC(50) 19 μM）和GABA类似物蝇蕈醇敏感的同聚通道。Hco-LGC-38通道对GABA的敏感性与果蝇RDL受体的报道值相似，而其对蝇蕈醇较低的敏感性与线虫GABA受体相似。Hco-LGC-38对通道阻滞剂印防己毒素也高度敏感，对氟虫腈和狄氏剂中度敏感。Hco-LGC-38的同源建模以及随后GABA和蝇蕈醇与结合位点的对接揭示了与结合位点残基的几种潜在相互作用，总体上似乎与其他无脊椎动物GABA受体的模型相似。
