12 research outputs found

    Role of serine 249 of ezrin in the regulation of sodium-dependent phosphate transporter NaPi-IIa activity in renal proximal tubular cells

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    Type IIa sodium-dependent phosphate transporter (NaPi-IIa) is responsible for renal phosphate reabsorption and maintenance of systemic phosphate homeostasis in mammals. Macromolecular complex formation of NaPi-IIa with sodium-proton exchanger related factor-1 (NHERF-1) and ezrin is important for apical membrane localization in the proximal tubular cells. Here, we investigated the interactions of the ezrin phosphomimetic mutation of serine to aspartic acid at 249 with NHERF-1 and the inhibition of apical membrane localization of NaPi-IIa. In vitro phosphorylation analysis revealed that serine 249 of human ezrin serves as a phosphorylation site for protein kinase A. The Nterminal half of ezrin had a dominant negative effect on the phosphate transport activity and inhibited the apical localization of NaPi-IIa in renal proximal tubular cells. We found that the phosphomimetic S249D mutant interfered with the inhibitory effects of the dominant negative mutant on the transport and localization of NaPi-IIa. The S249D mutant also inhibited the interaction with NHERF-1. Therefore, serine 249 of ezrin can play important roles in the regulation of the complex formation and membrane localization of NaPi-IIa

    Analysis of different complexes of type IIa sodium-dependent phosphate transporter in rat renal cortex using blue-native polyacrylamide gel electrophoresis

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    Type IIa sodium-dependent phosphate transporter (NaPi-IIa) can be localized in the apical plasma membrane of renal proximal tubule to carry out a rate-limiting step of phosphate reabsorption. For the apical localization, NaPi-IIa is required to form a macromolecular complex with some adaptor proteins such as Na+/H+ exchanger regulatory factor 1 (NHERF-1) and ezrin. However, the detail of macromolecular complex containing NaPi-IIa in the apical membrane of the renal proximal tubular cells has not been clarified. In this study, we identified at least four different complexes (220, 480, 920, 1,100 kDa) containing NaPi-IIa by using blue-native polyacrylamide gel electrophoresis. Interestingly, LC-MS/MS analysis and immunoprecipitation analysis reveal that megalin is a component of larger complexs (920 and 1,100 kDa). In addition, NaPi-IIa can be heterogeneously co-localized with ezrin and megalin on the apical membrane of renal proximal tubuler cells by fluorescence microscopy analysis. These results suggest that NaPi-IIa can form some different complexes on the apical plasma membrane of renal proximal tubular cells

    A Comparative Study on Recent Issues of the International Exchange System in Japanese Higher Education

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    publisher奈良国家間の相互依存関係の緊密化とともに、現代世界は名実ともに「国際化時代」を迎えつつある。こうした趨勢にあっては、とりわけ「高等教育機関の国際化」は、最も大きな的・質的変化を経験し、最も先端的な革新を迫られている部分であると思われる。 本研究では、かかる課題意識から、教育の「国際化」の諸側面のうち「教育交流制度の一環としての語学研修制度」を取り上げた。そして、国内およびアメリカの高等教育機関におけるその意義と現状、ならびに問題点を多面的に検討した。 その結果、本学において、今後、教育機会の空間的拡張(=国際化)戦略を推進する上で考慮すべき諸課題が浮かび上がったのである。また、アメリカにおける「語学研修サービス」の類型の抽出と、その妥当性についても併せて検討し、本学学生にとって最も望ましい「語学研修サービス」の在り方について、一定の結論を得た

    Identification of MMP1 as a novel risk factor for intracranial aneurysms in ADPKD using iPSC models.

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    Cardiovascular complications are the leading cause of death in autosomal dominant polycystic kidney disease (ADPKD), and intracranial aneurysm (ICA) causing subarachnoid hemorrhage is among the most serious complications. The diagnostic and therapeutic strategies for ICAs in ADPKD have not been fully established. We here generated induced pluripotent stem cells (iPSCs) from seven ADPKD patients, including four with ICAs. The vascular cells differentiated from ADPKD-iPSCs showed altered Ca[2+] entry and gene expression profiles compared with those of iPSCs from non-ADPKD subjects. We found that the expression level of a metalloenzyme gene, matrix metalloproteinase (MMP) 1, was specifically elevated in iPSC-derived endothelia from ADPKD patients with ICAs. Furthermore, we confirmed the correlation between the serum MMP1 levels and the development of ICAs in 354 ADPKD patients, indicating that high serum MMP1 levels may be a novel risk factor. These results suggest that cellular disease models with ADPKD-specific iPSCs can be used to study the disease mechanisms and to identify novel disease-related molecules or risk factors
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