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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Crucial role of copper in detection of metal-coordinating odorants
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Crucial role of copper in detection of metal-coordinating odorants

机译:铜在检测金属配位剂中的关键作用

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摘要

Odorant receptors (ORs) in olfactory sensory neurons (OSNs) mediate detection of volatile odorants. Divalent sulfur compounds, such as thiols and thioethers, are extremely potent odorants. We identify a mouse OR, MOR244-3, robustly responding to (methyl-thio)methanethiol (MeSCH_2SH; MTMT) in heterologous cells. Found specifically in male mouse urine, strong-smelling MTMT [human threshold 100 parts per billion (ppb)] is a semiochemical that attracts female mice. Nonadjacent thiol and thioether groups in MTMT suggest involvement of a chelated metal complex in MOR244-3 activation. Metal ion involvement in thiol-OR interactions was previously proposed, but whether these ions change thiol-mediated OR activation remained unknown. We show that copper ion among all metal ions tested is required for robust activation of MOR244-3 toward ppb levels of MTMT, structurally related sulfur compounds, and other metal-coordinating odorants (e.g., strong-smelling trans-cyclooctene) among >125 compounds tested. Copper chelator (tet-raethylenepentamine, TEPA) addition abolishes the response of MOR244-3 to MTMT. Histidine 105, located in the third transmem-brane domain near the extracellular side, is proposed to serve as a copper-coordinating residue mediating interaction with the MTMT-copper complex. Electrophysiological recordings of the OSNs in the septal organ, abundantly expressing MOR244-3, revealed neurons responding to MTMT. Addition of copper ion and chelator TEPA respectively enhanced and reduced the response of some MTMT-responding neurons, demonstrating the physiological relevance of copper ion in olfaction. In a behavioral context, an olfactory discrimination assay showed that mice injected with TEPA failed to discriminate MTMT. This report establishes the role of metal ions in mammalian odor detection by ORs.
机译:嗅觉感觉神经元(OSNs)中的气味受体(OR)介导挥发性气味的检测。二价硫化合物,例如硫醇和硫醚,是非常有效的增香剂。我们确定了小鼠OR,MOR244-3,对异源细胞中的(甲硫基)甲硫醇(MeSCH_2SH; MTMT)做出强烈反应。专门在雄性小鼠尿液中发现的强气味MTMT(人类阈值100亿分之十(ppb))是一种吸引雌性小鼠的化学信息素。 MTMT中不相邻的硫醇和硫醚基团表明,螯合的金属配合物参与了MOR244-3的活化。先前曾提出金属离子参与硫醇-OR相互作用,但是这些离子是否会改变硫醇介导的OR活化仍然未知。我们表明,测试的所有金属离子中的铜离子对于将MOR244-3朝着ppb水平的MTMT,结构上相关的硫化合物以及其他> 125种化合物中的其他金属配位增香剂(例如强气味的反式环辛烯)进行稳定活化是必需的经过测试。铜螯合剂(叔丁基亚乙基五胺,TEPA)的添加消除了MOR244-3对MTMT的反应。组氨酸105,位于细胞外侧附近的第三个跨膜结构域中,被提议用作介导与MTMT-铜复合物相互作用的铜配位残基。间隔器官中OSN的电生理记录,大量表达MOR244-3,表明神经元对MTMT有反应。铜离子和螯合剂TEPA的添加分别增强和减少了一些MTMT反应神经元的反应,表明铜离子在嗅觉中的生理相关性。在行为方面,嗅觉辨别分析表明注射TEPA的小鼠无法辨别MTMT。该报告确定了金属离子在ORs检测哺乳动物气味中的作用。

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    Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai E-Institute for Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China,Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine/Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences, Shanghai 200025, China;

    Department of Chemistry, University at Albany, State University of New York, Albany, NY 12222;

    Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai E-Institute for Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;

    Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104;

    Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai E-Institute for Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;

    Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai E-Institute for Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;

    Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai E-Institute for Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;

    Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai E-Institute for Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;

    Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai E-Institute for Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;

    Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104;

    Department of Chemistry, University at Albany, State University of New York, Albany, NY 12222;

    Department of Chemistry, University at Albany, State University of New York, Albany, NY 12222;

    Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104;

    Departments of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710,Departments of Neurobiology, Duke University Medical Center, Durham, NC 27710;

    Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai E-Institute for Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China,Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine/Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences, Shanghai 200025, China;

    Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai E-Institute for Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China,Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine/Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences, Shanghai 200025, China;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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