Ellison Michael, Haberlandt Christian, Gomez-Casati María Eugenia, Watkins Maren, Elgoyhen A Belén, McIntosh J Michael, Olivera Baldomero M
Department of Biology, University of Utah, Salt Lake City, Utah 84112-0840, USA.
Biochemistry. 2006 Feb 7;45(5):1511-7. doi: 10.1021/bi0520129.
The alpha9 and alpha10 nicotinic acetylcholine receptor (nAChR) subunits assemble to form the alpha9alpha10 nAChR subtype. This receptor is believed to mediate cholinergic synaptic transmission between efferent olivocochlear fibers and the hair cells of the cochlea. In addition alpha9 and/or alpha10 expression has been described in dorsal root ganglion neurons, lymphocytes, skin keratinocytes, and the pars tuberalis of the pituitary. Specific antagonists that selectively block the alpha9alpha10 channel could be valuable tools for elucidating its role in these diverse tissues. This study describes a novel alpha-conotoxin from the Western Atlantic species Conus regius, alpha-conotoxin RgIA (alpha-RgIA), that is a subtype specific blocker of the alpha9alpha10 nAChR. alpha-RgIA belongs to the alpha4/3 subfamily of the alpha-conotoxin family; sequence and subtype specificity comparisons between alpha-RgIA and previously characterized alpha4/3 toxins indicate that the amino acids in the C-terminal half of alpha-RgIA are responsible for its preferential inhibition of the alpha9alpha10 nAChR subtype.
α9和α10烟碱型乙酰胆碱受体（nAChR）亚基组装形成α9α10 nAChR亚型。据信该受体介导传出橄榄耳蜗纤维与耳蜗毛细胞之间的胆碱能突触传递。此外，已在背根神经节神经元、淋巴细胞、皮肤角质形成细胞和垂体结节部中描述了α9和/或α10的表达。选择性阻断α9α10通道的特异性拮抗剂可能是阐明其在这些不同组织中作用的有价值工具。本研究描述了一种来自西大西洋物种织锦芋螺的新型α-芋螺毒素，即α-芋螺毒素RgIA（α-RgIA），它是α9α10 nAChR的亚型特异性阻滞剂。α-RgIA属于α-芋螺毒素家族的α4/3亚家族；α-RgIA与先前表征的α4/3毒素之间的序列和亚型特异性比较表明，α-RgIA C端一半的氨基酸负责其对α9α10 nAChR亚型的优先抑制作用。
