Bicarbonate regulated adenylyl cyclase

碳酸氢盐调节的腺苷酸环化酶

基本信息

批准号：
7887627
负责人：
JOCHEN BUCK
金额：
$ 8.42万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-03 至 2010-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7887627
关键词：
Adenylate Cyclase Amino Acid Sequence Aqueous Humor Bicarbonate Ion Bicarbonate Ions Bicarbonates Biochemical Biological Blood flow Breathing Buffers C2 Domain Calcium Carbon Dioxide Catalytic Domain Cell Line Cells Cerebrospinal Fluid Chemoreceptors Cloning Collaborations Complement component C1s Cyanobacterium Cyclic AMP Data Diuresis Divalent Cations Enzymes Equilibrium Eubacterium Eukaryota Evolution Exhibits Family Frequencies Funding GTP-Binding Proteins Genetic Germ Cells Glucose Grant Hormone Responsive Hormones Immunoprecipitation Insulin Intercellular Fluid Kidney Knock-out Knowledge Laboratories Link Malaria Mammalian Cell Measures Mediating Metabolic Molecular Monoclonal Antibodies Nature Parasites Peptides Physiological Physiological Processes Process Property Protein Isoforms Proteins Protons Publishing Rattus Recombinants Regulation Research Personnel Second Messenger Systems Serum Signal Transduction Signaling Molecule Signaling Protein Somatic Cell Source Structure of beta Cell of islet System Testing Testis Tissues Universities Water Yeasts biological systems calcium bicarbonate carbonate dehydratase cell motility extracellular fungus inhibitor/antagonist male novel programs research study response second messenger sensor small molecule sperm cell

项目摘要

DESCRIPTION (provided by applicant): Multiple physiological processes (i.e., breathing, blood flow, cerebrospinal fluid and aqueous humor formation, and sperm activation) are modulated by carbon dioxide and/or bicarbonate. The only known mammalian signaling protein modulated by bicarbonate or carbon dioxide is the bicarbonate responsive 'soluble' adenylyl cyclase (sAC). Mammalian sAC enzymes are molecularly, biochemically, and structurally distinct from the G protein regulated transmembrane adenylyl cyclases which mediate cellular responses to hormones. With previous support from this grant, we have confirmed that sAC serves as a cellular sensor for extracellular bicarbonate in sperm and as a cellular sensor for extracellular pH (via fluctuations of intracellular bicarbonate) in the epidydymis. We now propose to continue this project by testing whether sAC serves as the bicarbonate and/or carbon dioxide sensor in other physiological processes. In preliminary data for this application we show that somatic cells express isoforms of bicarbonate responsive sAC distinct from those previously identified in male germ cells. We plan to: (1) purify the somatic forms of sAC from bicarbonate responsive tissues and cell lines and determine their peptide amino acid sequences. (2) Clone these novel sAC isoforms. (3) Characterize their biochemical properties using both the native enzymes and heterologously expressed, recombinant sAC isoforms. (4) Ascertain whether and which sAC isoforms are expressed in various bicarbonate/carbon dioxide regulated physiological systems.

描述（由申请人提供）：多种生理过程（即呼吸、血流、脑脊液和房水形成以及精子活化）由二氧化碳和/或碳酸氢盐调节。唯一已知的受碳酸氢盐或二氧化碳调节的哺乳动物信号蛋白是碳酸氢盐响应性“可溶性”腺苷酸环化酶（sAC）。哺乳动物 sAC 酶在分子、生物化学和结构上与介导细胞对激素反应的 G 蛋白调节的跨膜腺苷酸环化酶不同。在这笔资助之前的支持下，我们已经确认 sAC 作为精子细胞外碳酸氢盐的细胞传感器和附睾细胞外 pH 值（通过细胞内碳酸氢盐的波动）的细胞传感器。我们现在建议通过测试 sAC 是否在其他生理过程中充当碳酸氢盐和/或二氧化碳传感器来继续该项目。在该应用的初步数据中，我们表明体细胞表达碳酸氢盐反应性 sAC 的亚型，与之前在雄性生殖细胞中鉴定的亚型不同。我们计划：（1）从碳酸氢盐反应组织和细胞系中纯化sAC的体细胞形式，并确定其肽氨基酸序列。 (2) 克隆这些新的 sAC 同工型。 (3) 使用天然酶和异源表达的重组 sAC 亚型表征其生化特性。 (4)确定sAC亚型是否以及哪些sAC亚型在各种碳酸氢盐/二氧化碳调节的生理系统中表达。