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Investigation on determinants of substrate specificities of nucleotide-sugar transporters

核苷酸-糖转运蛋白底物特异性决定因素的研究

基本信息

批准号：
15570105
负责人：
ISHIDA Nobuhiro
金额：
$ 2.3万
依托单位：
Chiba Institute of Science, Faculty of Risk and Crisis Management (2005)Tokyo Metropolitan Organization for Medical Research (2003-2004)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

Nucleotide sugar transporters are very hydrophobic proteins ranging from 340 a.a. to 400 a.a. long. They reside in Golgi apparatus and/or ER membrane exposing their C- and N-terminal regions to cytosol, and are highly likely to have ten transmembrane helices. They antiport nucleotide sugars pooled in cytosol into lumen of Golgi apparatus and/or ER lumen with the corresponding nucleoside monophosphates. The transported nucleotide sugars are utilized as sugar donors by glycosyltransferases for synthesis of sugar chains of glycoproteins. glycolipids and polysaccharides.Nucleotide-sugar transporter genes constitute a gene family that was assigned as SLC (solute carrier)35 family by the HUGO gene nomenclature committee. We carried out data mining of the gene databank, and found 23 human genes which shows significant similarity each others. We classified them into 6 subfamilies, from A to F, based on their similarity, and provided the gene symbol to each of the genes.We had found hUGTrel8 (S … More LC35D2) gene that exhibits around 50% similarity with human SLC35D1 (UDP-glucuronic acid/UDP-N-acetylgalactosamine transporter), fruitfly fringe connection (frc) transporter, and nematode SQV-7 transporter, the latter two being involved in developmental and ontological processes. We demonstrated that SLC35D2 was localized in the Golgi apparatus and transported UDP-N-acetylglucosamine. These observations indicate that SLC35D2 is a good candidate for the ortholog of frc transporter.We also biochemically demonstrated that a Drosophila homolog of the human GDP-fucose transporter, the Golgi GDP-fucose transporter (Gfr), specifically transport GDP-fucose in vitro, and generated null mutants of Gfr in Drosophila. The phenotypes of the Drosophila Gfr mutants were rescued by the human GDP-fucose transporters. Hence, these null mutants are good Drosophila models of CDGIIc patients who have defective GDP-fucose transporter to investigate the possible cause of the developmental defects in the patients. Less

核苷酸糖转运蛋白是非常疏水的蛋白质，范围从340 a.a. 400 a.a.久了它们存在于高尔基体和/或ER膜中，将它们的C-和N-末端区域暴露于胞质溶胶，并且很可能具有十个跨膜螺旋。它们将胞质溶胶中汇集的核苷酸糖与相应的核苷一磷酸反向转运到高尔基体腔和/或ER腔中。转运的核苷酸糖被糖基转移酶用作糖供体，用于合成糖蛋白的糖链。核苷酸-糖转运蛋白基因构成被HUGO基因命名委员会指定为SLC（溶质载体）35家族的基因家族。我们对基因数据库进行了数据挖掘，发现了23个人类基因，这些基因之间具有显著的相似性。根据它们的相似性，我们将它们分为6个亚家族，从A到F，并为每个基因提供了基因符号。 ...更多信息 LC 35 D2）基因，其与人SLC 35 D1（UDP-葡萄糖醛酸/UDP-N-乙酰半乳糖胺转运蛋白）、果蝇边缘连接（frc）转运蛋白和线虫SQV-7转运蛋白表现出约50%的相似性，后两者参与发育和本体过程。我们证明了SLC 35 D2定位于高尔基体并转运UDP-N-乙酰葡萄糖胺。这些观察结果表明，SLC 35 D2是一个很好的候选人的直向同源物的frc transporter.我们还生化证明，果蝇同源的人GDP-岩藻糖转运蛋白，高尔基体GDP-岩藻糖转运蛋白（Gfr），在体外特异性运输GDP-岩藻糖，并产生无效突变体的Gfr在果蝇。果蝇Gfr突变体的表型被人GDP-岩藻糖转运蛋白拯救。因此，这些无效突变体是具有缺陷型GDP-岩藻糖转运蛋白的CDGIIc患者的良好果蝇模型，以研究患者中发育缺陷的可能原因。少

项目成果

期刊论文数量（26）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Ishida, N., Kawakita, M.: "Molecular physiology and pathology of the nucleotide sugar transporter family (SLC35)"Pflug.Arch.Eur.J.Phy.. 447・5. 768-775 (2004)

Ishida, N.，Kawakita, M.：“核苷酸糖转运蛋白家族（SLC35）的分子生理学和病理学” Pflug.Arch.Eur.J.Phy.. 768-775（2004）。

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

Hypoxia induces adhesion molecules on cancer cells: A missing link between Warburg effect and induction of selectin-ligand carbohydrates

DOI：
10.1073/pnas.0402088101
发表时间：
2004-05-25
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
影响因子：
11.1
作者：
Koike, T;Kimura, N;Kanangi, R
通讯作者：
Kanangi, R

Molecular physiology and pathology of the nucleotide sugar transporter family (SLC35)