Structure and function of polyamine transport systems and NMDA receptors

多胺转运系统和 NMDA 受体的结构和功能

• 批准号: 16590042
• 负责人: KASHIWAGI Keiko
• 金额: $ 2.3万
• 依托单位: Chiba Institute of Science (2005)Chiba University (2004)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590042/
• 关键词: Polyamine; Spermine; Spermidine; Polyamine transport; NMDA receptor; R-domain; Phosphorylation; post Golgi; 輸送; endocytosis; exocytosis; チャネルブロッカー; AQポリアミン

1.Polyamine transport in Saccharomyces cerevisiae was studied. (1)TPO1, located on the plasma membrane, catalyzed the excretion of polyamines. The transport activity of TPO1 was enhanced through phosphorylation at Ser^<19> protein kinase C and at Thr^<52> by casein kinase 1. Sorting of TPO1 from the endoplasmic reticulum to the plasma membrane was enhanced through phosphorylation at Ser^<342> by cAMP dependent protein kinases 1 and 2. (2)TPO5 encoded by YKL174c catalyzed the excretion of putrescine and spermidine, and it was localized on Golgi or post-Golgi secretory vesicles, suggesting that secretory and endocytic pathways, are involved in the excretion of polyamines by TPO5. (3)We found that urea transporter DUR3 and S-adenosylmethionine transporter SAM3, located on plasma membrane, catalyze polyamine uptake preferentially, and that the expression of both mRNAs were repressed by the presence of polyamines in medium.2.NMDA (N-methyl-D-aspartate) receptor is a subtype of glutamate rec … More eptors and involved in the plasticity of central nerves system. The effects of various anthraquinone polyamines (AQP) were studied at NMDA receptors expressed in Xenopus laevis oocytes. All AQP derivatives inhibited responses of NR1/NR2 receptors in oocytes voltage-clamped at -70 mV. The block was strongly voltage-dependent. AQ spermidine (AQ34) inhibited responses of NR1/NR2 receptors but did not inhibit responses of AMPA receptors indicating that AQ34 is preferential NMDA antagonists. Results of experiments using mutant NR1 and NR2 subunits identified residues that influence block by AQ34. These residues are located in the outer vestibule at the selectivity filter/narrowest constriction of the channel and in the inner vestibule below the level of the selectivity filter. Regulatory domain (R-domain) proteins of NMDA receptor subunits were purified and the properties of the proteins were determined. It was suggested that binding sites of spermine and ifenprodil on R-domain proteins are different each other. Less

1.研究了多胺在酿酒酵母中的转运。(1)位于质膜上的TPO1催化多胺的排泄。酪蛋白激酶1通过蛋白激酶C和酪蛋白激酶1的磷酸化增强了TPO1的转运活性。通过cAMP依赖的蛋白激酶1和2，TPO1从内质网到质膜的分离被增强。(2)YKL174c编码的TPO5催化腐胺和亚精胺的分泌，并定位于高尔基体或高尔基体后的分泌囊泡上，提示TPO5参与了多胺的分泌。(3)我们发现位于质膜上的尿素转运蛋白DUR3和S-腺苷蛋氨酸转运蛋白SAM3优先催化多胺摄取，并且这两种转运蛋白的表达都被介质中的多胺抑制。2.N-甲基-D-天冬氨酸受体是谷氨酸受体…的一个亚型。更多的受体参与中枢神经系统的可塑性。以非洲爪哇卵母细胞为材料，研究了不同的蒽醌多胺(AQP)对非洲爪哇卵母细胞NMDA受体表达的影响。所有AQP衍生物均抑制电压钳电压为-70 mV的卵母细胞NR1/NR2受体的反应。该模块与电压有很强的相关性。AQ亚精胺(AQ34)抑制NR1/NR2受体的反应，但不抑制AMPA受体的反应，提示AQ34是NMDA的选择性拮抗剂。使用突变的NR1和NR2亚基的实验结果确定了影响AQ34阻断的残基。这些残留物位于选择性过滤器/通道最窄狭窄处的外前庭和选择性过滤器水平以下的内前庭。纯化NMDA受体亚基的调节结构域(R结构域)蛋白，并对其性质进行测定。提示精胺和异丙苯地尔在R结构域蛋白上的结合部位各不相同。较少

项目成果

Structural and functional relationship among diamines in terms of inhibition of cell growth

• DOI: 10.1093/jb/mvh150
• 发表时间: 2004-10-01
• 期刊: JOURNAL OF BIOCHEMISTRY
• 影响因子: 2.7
• 作者: Higashi, K;Yoshida, K;Igarashi, K
• 通讯作者: Igarashi, K

Excretion and uptake of cadaverine by CadB and its physiological functions in Escherichia coli

• DOI: 10.1046/j.1365-2958.2003.03913.x
• 发表时间: 2004-03-01
• 期刊: MOLECULAR MICROBIOLOGY
• 影响因子: 3.6
• 作者: Soksawatmaekhin, W;Kuraishi, A;Igarashi, K
• 通讯作者: Igarashi, K

Excretion of putrescine and spermidine by the protein encoded by YKL174c (TPO5) in Saccharomyces cerevisiae.

酿酒酵母中 YKL174c (TPO5) 编码的蛋白质排泄腐胺和亚精胺。

• 发表时间: 2005
• 期刊: J.Biol.Chem. 280
• 作者: Tachihara;K. et al.
• 通讯作者: K. et al.

Polyamine oxidize and acrolein as novel biochemical markers for diagnosis of cerebral stroke

多胺氧化和丙烯醛作为诊断脑卒中的新型生化标志物

• 发表时间: 2005
• 期刊: Stroke 36
• 作者: Tomitori;H;et al.
• 通讯作者: et al.

Modulation of blood coagulation and fibrinolysis by polyamines in the presence of glycosaminoglycans

• DOI: 10.1016/j.biocel.2005.04.014
• 发表时间: 2005-09-01
• 期刊: INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
• 影响因子: 4
• 作者: Homma, R;Mase, A;Igarashi, K
• 通讯作者: Igarashi, K