Molecular mechanism for targeting of NCX1 to basolateral membrane in renal epithelial cells

NCX1靶向肾上皮细胞基底外侧膜的分子机制

• 批准号: 23590319
• 负责人: IWAMOTO Takahiro
• 金额: $ 3.33万
• 依托单位: Fukuoka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590319/
• 关键词: イオン輸送体; Ca2+シグナル; 腎上皮細胞; 腎機能; イオン輸送; 酵母two-hybrid; 蛋白質相互作用

Na+/Ca2+ exchanger type 1 (NCX1) bidirectionally exchanges 3 Na+ with 1 Ca2+, depending on the electrochemical gradients across the plasma membrane. In renal tubule, NCX1 is localized to the basolateral membranes of distal convoluted tubule cells, and is considered to be involved in Ca2+ reabsorption. However, the molecular mechanisms for its membrane sorting remain to be elucidated. In the present study, we found that the intracellular domain of NCX1 interacts with the adaptor protein. Using GST pull-down assays, we further identified the binding motif in NCX1 molecule. We also found that the mutations in the binding motif of NCX1 affect its membrane sorting in epithelial MDCK cells, suggesting the interaction between NCX1 and the adaptor protein plays a key role in NCX1 basolateral sorting.

Na+/Ca2+交换器类型1 （NCX1）双向交换3 Na+与1 Ca2+，这取决于跨质膜的电化学梯度。在肾小管中，NCX1定位于远曲小管细胞的基底外膜，并被认为参与Ca2+重吸收。然而，其膜分选的分子机制仍有待阐明。在本研究中，我们发现NCX1的胞内结构域与接头蛋白相互作用。通过GST下拉分析，我们进一步确定了NCX1分子中的结合基序。我们还发现NCX1结合基序的突变影响其在上皮MDCK细胞中的膜分选，这表明NCX1与接头蛋白之间的相互作用在NCX1基底外分选中起关键作用。

项目成果

Involvement of TRPC3/6 channels in myogenic tone regulation and A1-adrenoceptor-mediated vasoconstriction of murine mesenteric arteries

TRPC3/6 通道参与肌原张力调节和 A1 肾上腺素受体介导的小鼠肠系膜动脉血管收缩

• 发表时间: 2013
• 作者: Kita S;Horie I;Arai Y;Iwamoto T
• 通讯作者: Iwamoto T

Na^+/Ca^<2+> exchanger type-1 contributes to hypertension in pseudohypoaldosteronism type II and cushing's syndrome models

Na^ /Ca^<2 > 1 型交换器导致 II 型假性醛固酮增多症和库欣综合征模型中的高血压

• 发表时间: 2012
• 作者: Kita S;Uchida S;Komuro I;Iwamoto T
• 通讯作者: Iwamoto T

Na+/Ca2+交換輸送体をめぐるトランスポートソーム

涉及 Na+/Ca2+ 交换转运蛋白的转运体

• 发表时间: 2011
• 作者: 松末公彦;ら;藤原永年,中崇,前田伸司,柴田満,仁木満美子,大原直也,前山順一,矢野郁也,山本三郎;喜多紗斗美
• 通讯作者: 喜多紗斗美

ACTH誘発性およびPHAII型高血圧におけるNCX1の役割

NCX1 在 ACTH 诱发和 PHAII 型高血压中的作用

• 发表时间: 2011
• 作者: Nishioku T;Yamauchi A;Takata F;Watanabe T;Furusho K;Shuto H;Dohgu S;Kataoka Y;喜多紗斗美
• 通讯作者: 喜多紗斗美

Na+/Ca2+ Exchanger 1/2 Double-Heterozygote Knockout Mice Display Increased Nitric Oxide Component and Altered Colonic Motility

• DOI: 10.1254/jphs.13114fp
• 发表时间: 2013-11-01
• 期刊: JOURNAL OF PHARMACOLOGICAL SCIENCES
• 影响因子: 3.5
• 作者: Nishiyama, Kazuhiro;Azuma, Yasu-Taka;Takeuchi, Tadayoshi
• 通讯作者: Takeuchi, Tadayoshi