BRAIN ALPHA-BUNGAROTOXIN BINDING-PROTEIN CDNAS AND MABS REVEAL SUBTYPES OF THIS BRANCH OF THE LIGAND-GATED ION CHANNEL GENE SUPERFAMILY

BRAIN ALPHA-BUNGAROTOXIN BINDING-PROTEIN CDNAS AND MABS REVEAL SUBTYPES OF THIS BRANCH OF THE LIGAND-GATED ION CHANNEL GENE SUPERFAMILY
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DOI:
10.1016/0896-6273(90)90031-a
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发表时间:
1990-07-01
期刊:
影响因子:
16.2
通讯作者:
LINDSTROM, J
LINDSTROM, J
中科院分区:
医学1区
文献类型:
--
作者:
SCHOEPFER, R;CONROY, WG;LINDSTROM, J

文献摘要

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a- bungarotoxin (aBgt)是一种有效的、高亲和力的肌肉烟碱乙酰胆碱受体(achr)拮抗剂,但对神经元的achr无效。肌肉和神经元的乙酰胆碱还原酶都被认为是由排列在中心阳离子通道周围的多个同源亚基形成的,其开放受乙酰胆碱结合的调节。相比之下,在鸟类和哺乳动物神经元中发现的高亲和力aBgt结合蛋白(aBgtBPs)的确切结构和功能尚不清楚。本研究表明,编码aBgtBP al和a2亚基的cDNA克隆将aBgtBP定义为配体门控离子通道8ene超家族中的基因家族成员,但与来自肌肉和神经的achr基因家族不同。针对细菌表达的aBgtBP al和a2亚基片段建立的亚基特异性单克隆抗体显示,在胚胎第18天的鸡脑中存在至少两种不同的aBgtBP亚型。超过75%的aBgtBP具有al亚基,但不具有a2亚基,较小的aBgtBP亚型(~,15%)同时具有al和a2亚基。
Summary a-Bungarotoxin (aBgt) is a potent, high-affinity antagonist for nicotinic acetylcholine receptors (AChRs) from muscle, but not for AChRs from neurons. Both muscle and neuronal AChRs are thought to be formed from multiple homologous subunits aligned around a central cation channel whose opening is regulated by ACh binding. In contrast, the exact structure and function of highaffinity aBgt binding proteins (aBgtBPs) found in avian and mammalian neurons remain unknown. Here we show that cDNA clones encoding aBgtBP al and a2 subunits define aBgtBPs as members of a gene family within the ligand-gated ion channel 8ene superfamily, but distinct from the gene families of AChRs from muscles and nerves. Subunit-specific monoclonal antibodies raised against bacterially expressed aBgtBP al and a2 subunit fragments reveal the existence of at least two different aBgtBP subtypes in embryonic day 18 chicken brains. More than 75% of all aBgtBPs have the al subunit, but no a2 subunit, and a minor aBgtBP subtype (~, 15%) has both the al and a2 subunits.