Function and regulatory system of water transporting aquaporin channels

2009 Fiscal Year Final Research Report

• Project/Area Number: 17GS0312
• Research Category: Grant-in-Aid for Creative Scientific Research
• Allocation Type: Single-year Grants
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: SASAKI Sei Tokyo Medical and Dental University, 医歯学総合研究科, 教授 (60170677)
• Co-Investigator(Kenkyū-buntansha): ISHIBASHI Kenichi 明治薬科大学, 薬学部, 教授 (80223022) ; UCHIDA Sinichi 東京医科歯科大学, 医歯学総合研究科, 准教授 (50262184) ; KOBAYASHI Katsuki 国立病院機構千葉東病院, 臨床研究センター, 室長 (40415451) ; NODA Yumi 東京医科歯科大学, 医歯学総合研究科, 特任准教授 (30372436)
• Project Period (FY): 2005 – 2009
• Keywords: 水チャネル / アクアポリン / 水輸送

Research Abstract

Physiological roles of AQPs were investigated by generating and analyzing AQP gene targetting mice. Regulatory mechanisms of AQPs were also clarified by identifying AQP-binding protein complexes. These results shed light on development of new drugs modulating the functions of AQPs.

Research Products

• [Journal Article] Targeted disruption of the Wnk4 gene decreases phosphorylation of Na-Cl cotransporter, increases Na excretion and lowers blood pressure (2009)
  • Author(s): Ohta A, Rai T, Yui N, Chiga M, Yang SS, Lin SH, Sohara E, Sasaki S, Uchida S.
  • Journal Title: Hum.Mol.Genet. 18 Pages: 3978-86
• [Journal Article] Pancreas-specific aquaporin 12 null mice showed increased susceptibility to caerulein-induced acute pancreatitis (2009)
  • Author(s): Ohta E, Itoh T, Nemoto T, Kumagai J, Ko SB, Ishibashi K, Ohno M, Uchida K, Ohta A, Sohara E, Uchida S, Sasaki S, Rai T.
  • Journal Title: Am.J.Physiol.Cell Physiol. 297 Pages: 1368-78
• [Journal Article] FAPP2 is required for aquaporin-2 apical sorting at trans-Golgi network in polarized MDCK cells (2009)
  • Author(s): Yui N, Okutsu R, Sohara E, Rai T, Ohta A, Noda Y, Sasaki S, Uchida S.
  • Journal Title: Am.J.Physiol.Cell Physiol. 297 Pages: 1389-1396
• [Journal Article] Reciprocal interaction with G-actin and tropomyosin is essential for aquaporin-2 trafficking (2008)
  • Author(s): Noda Y, Horikawa S, Kanda E, Yamashita M, Meng H, Eto E, Li Y, Kuwahara M, Hirai K, Pack C, Kinjo M, Okabe S, Sasaki S.
  • Journal Title: J.Cell Biol. 182 Pages: 587-601
• [Journal Article] Molecular pathogenesis of pseudohypoaldosteronism type II : generation and analysis of a Wnk4 D561A/+ knock-in mouse model (2007)
  • Author(s): Yang SS, Morimoto T, Rai T, Chiga M, Sohara E, Ohno M, Uchida K, Lin S-H, Moriguchi T, Shibuya H, Kondo Y, Sasaki S, Uchida S.
  • Journal Title: Cell Metab 5 Pages: 331-344
• [Journal Article] The polarized trafficking of the aquaporin-3 water channel is mediated by an N-Terminal Sorting Signal (2006)
  • Author(s): Rai T, Sasaki S, Uchida S.
  • Journal Title: Am J Physiol Cell Physiol. 290(1) Pages: C298-304
• [Journal Article] Pathogenesis and treatment of autosomal-dominant nephrogenic diabetes insipidus caused by an aquaporin 2 mutation (2006)
  • Author(s): Sohara E, Rai T, Yang SS, Uchida K, Nitta K, Horita S, Ohno M, Harada A, Sasaki S, Uchida S.
  • Journal Title: Proc Natl Acad Sci USA 103 Pages: 14217-14222
• [Journal Article] Progressive adipocyte hypertrophy in aquaporin-7 deficient mice : Adipocyte glycerol permeability as a novel regulator of fat accumulation (2005)
  • Author(s): Hara-Chikuma M, Sohara E, Rai T, Ikawa M, Okabe M, Sasaki S, Uchida S, Verkman AS.
  • Journal Title: J Biol Chem. 280(16) Pages: 15493-15496
• [Journal Article] Disruption of aquaporin-11 produces polycystic kidneys following vacuolization of the proximal tubule (2005)
  • Author(s): Morishita Y, Matsuzaki T, Hara-Chikuma M, Ando A, Shimono M, Matsuki A, Kobayashi K, Ikeda M, Yamamoto T, Verkman A, Kusano E, Ookawara S, Takata K, Sasaki S, Ishibashi K.
  • Journal Title: Mol Cell Biol. 25 Pages: 7770-7779
• [Journal Article] Identification of a multiprotein "motor" complex binding to water channel aquaporin-2 (2005)
  • Author(s): Noda Y, Horikawa S, Katayama Y, Sasaki S.
  • Journal Title: Biochem Biophys Res Commun. 330 Pages: 1041-1047
• [Journal Article] Defective water and glycerol transport in the proximal tubules of AQP7 knockout mice (2005)
  • Author(s): Sohara E, Rai T, Miyazaki J, Verkman AS, Sasaki S, Uchida S.
  • Journal Title: Am J Physiol Renal Physiol. 289(6) Pages: F1195-1200
• [Presentation] Targeted disruption of pancreatic-specific water-Channel, aquaporin-12, results in increased susceptibility to drug-induced acute pancreatitis (2009)
  • Author(s): Ohta E, Itoh T, Nemoto T, Kumagai J, Ko S, Ishibashi K, Kawashima M, Uchida K, Ohta A, Rai T, Uchida S, Sasaki S.
  • Organizer: World Congress of Nephrology 2009
  • Place of Presentation: Milan
  • Year and Date: 20090500
• [Presentation] Reciprocal interaction with G-Actin and tropomyosin is critical for AQP2 translocation to the apical membrane (2008)
  • Author(s): Noda Y, Li Y, Eto K, Horikawa S, Sasaki S.
  • Organizer: The 41st Annual Meeting of American Society of Nephrology
  • Place of Presentation: Philadelphia
  • Year and Date: 20081100
• [Presentation] Neonatal kidneys of AQP11-disrupted mice exhibit enhanced apotosis followed by a remarkable slowing of cyst-formation by rapamycin treatment (2007)
  • Author(s): Kobayashi K, Ishibashi K, Sasaki S.
  • Organizer: The 5^<th> International Conference of Aquaporin
  • Place of Presentation: Nara
  • Year and Date: 20070700
• [Presentation] Comparison between AQP2 and ENaC in intracellular trafficking (2007)
  • Author(s): Meng H, Noda Y, Yamashita M, Hirai K, Horikawa S, Sasaki S.
  • Organizer: The 5^<th> International Conference of Aquaporin
  • Place of Presentation: Nara
  • Year and Date: 20070700
• [Presentation] Defective water and glycerol transport in the proximal tubules of AQP7 knockout mice (2005)
  • Author(s): Sohara E, Rai T, Verkman A. S., Sasaki S, Uchida S.
  • Organizer: 38^<th> Annual Meeting of American Society of Nephrology
  • Place of Presentation: Philadelphia
  • Year and Date: 2005-11-11
• [Book] 水とアクアポリンの生物学 (2008)
  • Author(s): 佐々木成, 編
  • Total Pages: 216
  • Publisher: 中山書店
• [Book] からだと水の事典 (2008)
  • Author(s): 佐々木成, 石橋賢一, 編
  • Total Pages: 7-8, 34-38, 64-70, 179
  • Publisher: 朝倉書店
• [Book] みずみずしい体のしくみ (2005)
  • Author(s): 佐々木成, 編
  • Total Pages: 183
  • Publisher: クバプロ
• [Remarks] ホームページ
  • URL: http://www.tmd.ac.jp/grad/kid/aquaporin/index.html