Importance of copper chaperone Cox17p in early embryogenesis.

铜伴侣 Cox17p 在早期胚胎发生中的重要性。

基本信息

批准号：
15370050
负责人：
KAKO Koichiro
金额：
$ 4.16万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15370050/
关键词：
Cox17p mitochondria cytochrome c oxidase Sco1 2p central nervous system in situ hybridization 細胞内銅輸送機構

项目摘要

It is well known that the deficiencies in cytochrome c oxidase (CCO) are relatively rare but most often lethal. CCO, one of the mitochodrial respiratory enzymes, requires Cu (I) to express its enzymatic activity. Cox17p, Scolp, and its homologue Sco2p are thought to be involved in mitochondrial transport of copper to CCO. By in vitro GST-pull down assay, both Sco1p and Sco2p interact with Cox17p. Furthermore, Cox17p, Scolp and Sco2p also interact with Cox2p, a subunit of the binuclear-copper centre Cu_A of CCO. Northern blot analysis demonstrated that Cox17p, Sco1p and Sco2p are widely expressed at varying levels in a variety of mouse tissues including brain. Using in situ hybridization histochemistry, we characterized the expression profiles for these molecules in different regions of the normal adult mouse brain. The highest levels of these messages were associated with distinct neuronal subtypes, including pyramidal cell layers of hippocampus and ventral cochlear nucleus of pons, that were also contained high levels of CCO activity. Although CCO activities and expression levels of Cox17p and Scolp were relatively high, the expression of Sco2p was quite low in some subsets of neurons such as cerebellum Purkinje cells. It was thought that the difference of expression profile between Sco1p and Sco2p is originated in that of genomic structures, especially the promoter regions.

众所周知，细胞色素 C 氧化酶 (CCO) 缺陷相对罕见，但通常是致命的。 CCO 是一种线粒体呼吸酶，需要 Cu (I) 来表达其酶活性。 Cox17p、Scolp 及其同源 Sco2p 被认为参与线粒体将铜转运至 CCO。通过体外 GST-pull down 测定，Sco1p 和 Sco2p 均与 Cox17p 相互作用。此外，Cox17p、Scolp 和 Sco2p 还与 Cox2p（CCO 双核铜中心 Cu_A 的亚基）相互作用。 Northern blot分析表明Cox17p、Sco1p和Sco2p在包括大脑在内的多种小鼠组织中以不同水平广泛表达。使用原位杂交组织化学，我们表征了这些分子在正常成年小鼠大脑不同区域中的表达谱。这些信息的最高水平与不同的神经元亚型相关，包括海马锥体细胞层和脑桥腹侧耳蜗核，它们也含有高水平的 CCO 活性。尽管 CCO 活性以及 Cox17p 和 Scolp 的表达水平相对较高，但 Sco2p 在某些神经元亚群（如小脑浦肯野细胞）中的表达相当低。人们认为Sco1p和Sco2p表达谱的差异源于基因组结构的差异，特别是启动子区域。