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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 余明俊(Ming-Jiun Yu) | |
dc.contributor.author | Po-Jen Wang | en |
dc.contributor.author | 王柏人 | zh_TW |
dc.date.accessioned | 2021-06-16T13:05:46Z | - |
dc.date.available | 2018-09-24 | |
dc.date.copyright | 2013-09-24 | |
dc.date.issued | 2013 | |
dc.date.submitted | 2013-08-02 | |
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Uawithya, P., et al., Transcriptional profiling of native inner medullary collecting duct cells from rat kidney. Physiol Genomics, 2008. 32(2): p. 229-53. 38. Pisitkun, T., et al., High-throughput identification of IMCD proteins using LC-MS/MS. Physiol Genomics, 2006. 25(2): p. 263-76. 39. Khositseth, S., et al., Quantitative protein and mRNA profiling shows selective post-transcriptional control of protein expression by vasopressin in kidney cells. Mol Cell Proteomics, 2011. 10(1): p. M110 004036. 40. Yu, M.J., et al., Large-scale quantitative LC-MS/MS analysis of detergent-resistant membrane proteins from rat renal collecting duct. Am J Physiol Cell Physiol, 2008. 295(3): p. C661-78. 41. Yu, M.J., et al., LC-MS/MS analysis of apical and basolateral plasma membranes of rat renal collecting duct cells. Mol Cell Proteomics, 2006. 5(11): p. 2131-45. 42. Tonikian, R., et al., A specificity map for the PDZ domain family. PLoS Biol, 2008. 6(9): p. e239. 43. Knepper, M.A. and S. Nielsen, Kinetic model of water and urea permeability regulation by vasopressin in collecting duct. Am J Physiol, 1993. 265(2 Pt 2): p. F214-24. 44. Noda, Y., et al., Reciprocal interaction with G-actin and tropomyosin is essential for aquaporin-2 trafficking. J Cell Biol, 2008. 182(3): p. 587-601. 45. Park, E.J., et al., The role of 70-kDa heat shock protein in dDAVP-induced AQP2 trafficking in kidney collecting duct cells. Am J Physiol Renal Physiol, 2013. 304(7): p. F958-71. 46. Tamma, G., et al., Functional involvement of Annexin-2 in cAMP induced AQP2 trafficking. Pflugers Arch, 2008. 456(4): p. 729-36. 47. Tamma, G., et al., cAMP-induced AQP2 translocation is associated with RhoA inhibition through RhoA phosphorylation and interaction with RhoGDI. J Cell Sci, 2003. 116(Pt 8): p. 1519-25. 48. Noda, Y., et al., Aquaporin-2 trafficking is regulated by PDZ-domain containing protein SPA-1. FEBS Lett, 2004. 568(1-3): p. 139-45. 49. Moskalenko, S., et al., The exocyst is a Ral effector complex. Nat Cell Biol, 2002. 4(1): p. 66-72. 50. Dephoure, N., et al., A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A, 2008. 105(31): p. 10762-7. 51. Yui, N., et al., AQP2 is necessary for vasopressin- and forskolin-mediated filamentous actin depolymerization in renal epithelial cells. Biol Open, 2012. 1(2): p. 101-8. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/61556 | - |
dc.description.abstract | 腎臟集尿管細胞會受到抗利尿激素(antidiuretic hormone vasopressin)的刺激而調節腎臟對於水分的排除。 抗利尿激素可促使細胞中的第二型水通道蛋白(aquaporin-2, AQP2)由細胞內液胞轉運到細胞頂膜(apical plasma membrane)上,使得尿液中的水分通過頂膜而回到細胞間質中,藉此減少水分的排除。 抗利尿激素會改變AQP2羧基末端上四個磷酸化位點的磷酸化情形。 其中, vasopressin的刺激會促使AQP2上的serine 269位點被磷酸化,使得serine 269磷酸化的AQP2大量增加並停留在頂膜上。 然而,造成serine 269磷酸化的AQP2停留在頂膜上的分子基礎是完全未知的。 因為serine 269位於AQP2羧基末端的PDZ motif中,所以我們系統性的分析在大鼠急尿管細胞以及小鼠集尿管細胞株(mpkCCD)中,能夠藉由擁有特定的PDZ domain而與AQP2 PDZ motif結合的蛋白質有哪些。 在這兩種細胞中能共同找到4種擁有PDZ domain並且表現於頂膜上的蛋白質,分別為SIPA1L1,GOPC,MPP5,以及PDZRN3。 我們藉由生物資訊方法預測出SIPA1L1,GOPC以及MPP5可能結合的PDZ motif很相似於AQP2羧基末端的PDZ motif。 其中,減少SIPA1L1蛋白質在mpkCCD中的表現量時,即使在沒有vasopressin的刺激下,AQP2依然能夠出現在頂膜上,顯示SIPA1L1可能調控AQP2的內吞作用。 另外,我們發現serine 269去磷酸化的AQP2比模擬serine 269磷酸化的AQP2更能夠與SIPA1L1結合。 同樣地,serine 269去磷酸化的合成胜肽比模擬磷酸化的胜肽更能夠與SIPA1L1結合,暗示著SIPA1L1較能夠促進serine 269去磷酸化的AQP2的內吞作用。 進一步地我們發現當減少細胞中SIPA1L1蛋白質表現量時,在沒有vasopressin的刺激之下,serine 269去磷酸化的AQP2並非出現在細胞內液胞中而是出現在頂膜上。 然而,模擬serine 269磷酸化的AQP2則不受SIPA1L1表現量下降的影響而停留在頂膜上。 因此,我們的研究顯示AQP2的serine 269的磷酸化可能藉由減少其與SIPA1L1的交互作用, 使得serine 269 磷酸化的AQP2的內吞作用無法進行,因而造成其能夠停留在頂膜上。 | zh_TW |
dc.description.abstract | Renal water excretion is regulated by the collecting duct cells in response to the antidiuretic hormone vasopressin. Vasopressin induces translocation of water channel protein aquaporin-2 (AQP2) from intracellular vesicles to the apical plasma membrane of the cells where AQP2 transports water from the forming urine to the interstitium thereby reducing water excretion. Vasopressin changes AQP2 phosphorylation at four sites in the COOH terminus. Among them, serine 269 phosphorylation is strongly up-regulated by vasopressin and results in apical retention of AQP2. However, the molecular basis for serine 269 phosphorylation mediated apical AQP2 retention is largely unknown. Because serine 269 is located in the PDZ motif, we systematically analyzed PDZ domain-containing proteins expressed in rat and cultured mouse collecting duct cells (mpkCCD). Four apically expressed PDZ domain-containing proteins (SIPA1L1, GOPC, MPP5, and PDZRN3) were identified. Bioinformatic analysis predicted that SIPA1L1, GOPC, and MPP5 binds PDZ motifs that are similar to the AQP2 COOH-terminal PDZ motif. Co-imunoprecipitation results showed that SIPA1L1 bound AQP2 protein. SIPA1L1 knockdown resulted in apical localization of wild type AQP2 (AQP2-WT) in the mpkCCD cells in the absence of the vasopressin analog dDAVP, suggesting a role of SIPA1L1 in AQP2 internalization. Compared with phosphorylation-mimicking AQP2 mutant (AQP2-S269D), phosphorylation-ablated AQP2 mutant (AQP2-S269A) had a higher binding preference for SIPA1L1, suggesting a preferential binding of SIPA1L1 with AQP2 when serine 269 is not phosphorylated. Pull down experiments showed that SIPA1L1 preferred binding with synthetic peptide without serine 269 phosphorylation. These observations suggest that SIPA1L1 may facilitate AQP2 internalization when serine 269 is not phosphorylated. Thus, SIPA1L1 knockdown resulted in apical localization of serine 269 phosphorylation ablated AQP2 mutant in the absence of dDAVP. SIPA1L1 knockdown had no effect on apical localization of serine 269 phosphorylation mimicking AQP2 mutant. Collectively, our data suggested that vasopressin-induced serine 269 phosphorylation of AQP2 reduces its internalization by SIPA1L1. As a result, serine 269 phosphorylated AQP2 can retain on the apical plama membrane. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T13:05:46Z (GMT). No. of bitstreams: 1 ntu-102-R00442030-1.pdf: 6187443 bytes, checksum: 043f4713ee2a4fc33131eb60798e535e (MD5) Previous issue date: 2013 | en |
dc.description.tableofcontents | 誌謝 I
中文摘要 II Abstract III Introduction 1 Materials 5 Methods 12 Results 21 Serine 269 Phosphorylated Aquaporin-2 Locates in the Apical Plasma Membrane of MpkCCD Cells 21 Phosphorylation Mimicking AQP2-S269D Mutant Retains in the Apical Membrane in the Absence of dDAVP 23 Systematically Identification of Potential AQP2-Interacting PDZ Domain Proteins 25 Expression of SIPA1L1, GOPC, and MPP5 in mpkCCD cells 27 SIPA1L1 Interacts with AQP2 and Mediates AQP2 Endocytosis 28 AQP2 Serine 269 Phosphorylation Reduces It Interaction with SIPA1L1 and AQP2 Internalization 29 Discussion 31 Figures and Legends 35 Table 45 References 46 | |
dc.language.iso | en | |
dc.title | mpkCCD細胞中第二型水通道蛋白的Serine 269磷酸化減少SIPA1L1對其進行內吞作用 | zh_TW |
dc.title | Aquaporin-2 Serine 269 Phosphorylation Reduces Its Internalization by SIPA1L1 in mpkCCD Cells | en |
dc.type | Thesis | |
dc.date.schoolyear | 101-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 林水龍(Shuei-Liong Lin),李明學(Ming-Shyue Lee),李芳仁(Fang-Jen Lee) | |
dc.subject.keyword | 第二型水通道蛋白,磷酸化,內吞作用, | zh_TW |
dc.subject.keyword | Aquaporin-2,Phosphorylation,Internalization, | en |
dc.relation.page | 49 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2013-08-02 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
顯示於系所單位: | 生物化學暨分子生物學科研究所 |
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