GAS-1:: A mitochondrial protein controls sensitivity to volatile anesthetics in the nematode Caenorhabditis elegans
GAS-1:: A mitochondrial protein controls sensitivity to volatile anesthetics in the nematode Caenorhabditis elegans
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DOI：
10.1097/00000542-199902000-00031
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发表时间：
1999-02-01
期刊：
影响因子：
8.8
通讯作者：
Sedensky, MM
中科院分区：
文献类型：
--
作者：
Kayser, EB;Morgan, PG;Sedensky, MM
背景：秀丽隐杆线虫几个基因的突变改变了对挥发性麻醉剂的敏感性。一个基因gas-1（fc21）的突变导致动物在所有挥发性麻醉剂的浓度低于野生型时不能动弹，并且它不依赖于其他基因的突变来控制麻醉剂的敏感性。Gas-1对异氟烷的立体异构体具有不同的敏感性，因此可能是挥发性麻醉剂的直接靶点。作者克隆并鉴定了gas-1基因和突变等位基因fc21。方法：线虫遗传学技术如前所述。通过标准方法进行聚合酶链反应、测序和其他分子生物学技术。通过将DNA片段注射到突变动物的性腺中并对后代的突变表型损失进行评分来进行突变拯救。蛋白质GAS-1是线粒体NADH：泛醌氧化还原酶（呼吸链复合物I）的49-kDa（TP）亚基的同源物。gas-1（fc21）是一个错义突变，将一个严格保守的精氨酸替换为赖氨酸。结论：复合物I的49-kDa（IP）亚基的功能尚不清楚。复合物I的突变增加了秀丽隐杆线虫对挥发性麻醉剂的敏感性，这一发现可能涉及麻醉剂敏感性测定中的生理过程。具有gas-1基因突变的动物的超敏反应可能由对线粒体蛋白的直接麻醉作用或由线粒体功能障碍引起的其他部位的继发作用引起。
Background: Mutations in several genes of Caenorhabditis elegans confer altered sensitivities to volatile anesthetics. A mutation in one gene, gas-1(fc21), causes animals to be immobilized at lower concentrations of all volatile anesthetics than in the wild-type, and it does not depend on mutations in other genes to control anesthetic sensitivity. gas-1 confers different sensitivities to stereoisomers of isoflurane, and thus may be a direct target for volatile anesthetics. The authors have cloned and characterized the gas-1 gene and the mutant allele fc21.Methods: Genetic techniques for nematodes were as previously described. Polymerase chain reaction, sequencing, and other molecular biology techniques were performed by standard methods. Mutant rescue was done by injecting DNA fragments into the gonad of mutant animals and scoring the offspring for loss of the mutant phenotype.Results: The gas-1 gene was cloned and identified. The protein GAS-1 is a homologue of the 49-kDa (TP) subunit of the mitochondrial NADH:ubiquinone-oxidoreductase (complex I of the respiratory chain). gas-1(fc21) is a missense mutation replacing a strictly conserved arginine with lysine.Conclusions: The function of the 49-kDa (IP) subunit of complex I is unknown. The finding that mutations in complex I increase sensitivity of C, elegans to volatile anesthetics may implicate this physiologic process in the determination of anesthetic sensitivity. The hypersensitivity of animals with a mutation in the gas-1 gene may be caused by a direct anesthetic effect on a mitochondrial protein or secondary effects at other sites caused by mitochondrial dysfunction.