Molecular Mechanism in Mobilization of Proton Pump to Apical Cell Membrane of Gastric Parietal Cells

质子泵动员胃壁细胞顶细胞膜的分子机制

• 批准号: 06454149
• 负责人: KAWAMURA Masaru
• 金额: $ 4.1万
• 依托单位: University of Occupational and Environmental Health
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06454149/
• 关键词: H^+; K^+-ATPase; Na^+; chimera; oocyte; NA^+

The molecular mechanism involved in targeting of proton pump molecules to apical cell membrane of gastric parietal cells was studied. The Na-pump that is restricted basolaterally was examined in contrast.1. Assembly of the alpha-and beta-subunits is pre-requisite for targeting of the alpha-subunit to cell membranes. The disulfide-bonded loops in the extracellular domain of the beta-subunit and N-terminal domain of the alpha-subunit are involved in the assembly.2. The beta-subunit is interchangable between proton-and Na-pumps with respect to assembly with the alpha-subunit, but resulting hibrids are functionally inactive.Chimeric beta-subunits were constructed in order to assign specific site (s) of each beta-subunit. The specific sites are distributed in the extracellular domain of the beta-subunit.3. The first disulfide-bonded loop (L_1) in the extracellular domain is one of the specific sites. The 148th amino acid residue within L_1 is especially important.4. These results are summarized in our review.

研究了质子泵分子靶向胃壁细胞顶端细胞膜的分子机制。对基底外侧受限的钠泵进行了对比检查。α-和β-亚基的组装是α-亚基靶向细胞膜的先决条件。β亚基的胞外结构域和α亚基的N端结构域中的二硫键环参与组装.β-亚基在质子泵和Na泵之间可互换，与α-亚基组装，但产生的杂交体在功能上是无活性的。特异性位点分布在β亚基的胞外区。胞外区的第一个二硫键环（L_1）是其中一个特异性位点。L_1中第148位氨基酸残基尤为重要。这些结果总结在我们的审查。

项目成果

Susumu Ueno: "Significance of the β-subunit in the Biogenesis of Na^+/K^+-ATPase" Bioscience Reports. (印刷中). (1997)

Susumu Ueno：“β-亚基在 Na^+/K^+-ATP 酶生物发生中的意义”生物科学报告（1997 年出版）。

Michiaki Morohashi: "Expression of (Na,K) ATPase/Ca-ATPase Chimeric Proteins in Xenopus Oocytes Revealed that the COOH-terminal One-third of the (Na,K) ATPase α-subunit is Involved in Assembly with the β-subunit." J. UOEH. 16. 277-286 (1994)

Michiaki Morohashi：“(Na,K) ATPase/Ca-ATPase 嵌合蛋白在非洲爪蟾卵母细胞中的表达表明，COOH 末端三分之一的 (Na,K) ATPase α 亚基参与与 β 亚基的组装” J. UOEH. 16. 277-286 (1994)

Michiaki Morohashi: "Expression of (Na, K) ATPase/Ca-ATPase Chimeric Proteins in Xenopus Oocytes Revealed that the COOH-terminal One-third of the (Na, K) ATPase alpha-subunit is Involved in Assembly with the beta-subunit." J.Uoeh. 16. 277-286 (1994)

Michiaki Morohashi：“(Na, K) ATPase/Ca-ATPase 嵌合蛋白在非洲爪蟾卵母细胞中的表达表明，COOH 末端三分之一的 (Na, K) ATPase α 亚基参与与 β 亚基的组装

Suzumu Ueno: "Functional Consequences of Substitution of the Disulfide-Bonded Segment, Cys127-Cys150, Located in the Extracellular Domain of the Na, K-ATPase beta-subunit : Arg148 is Essential for the Functional Expression of Na, K-ATPase." J.Biochem. 117

Suzumu Ueno：“位于 Na, K-ATP 酶 β 亚基胞外域的二硫键片段 Cys127-Cys150 取代的功能后果：Arg148 对于 Na, K-ATP 酶的功能表达至关重要。”

Shunsuke Noguchi: "The functional roles of disulfide bonds in the β-subunit of (Na,K) ATPase as studied by site-directed mutagenesis." FEBS Lett.341. 233-238 (1994)

Shunsuke Noguchi：“通过定点诱变研究二硫键在 (Na,K) ATP 酶亚基中的功能作用。”FEBS Lett.341 (1994)。