Role of aquaporins in endoplasmic reticulum

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659413
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Kidney internal medicine
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: SASAKI SEI 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (60170677)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 水・電解質代謝学 / 水チャネル / 遺伝子改変マウス

Research Abstract

The purpose of our study was to clarify pathopysiologival roles of aquaporins in endoplasmic reticulum (ER). AQP11 knockout mice (AQP11-KO) showed polycystic kidney. However, molecular mechanism(s) of the cyst formation remained to be determined. To clarify this, we generated HA-tagged AQP11 BAC transgenic mice (AQP11-TG), and also analyzed AQP11-KO focusing on PKD1 (PC-1)and PKD2 (PC-2). AQP11 was found to be localized in endoplasmic reticulum in the proximal tubules, and impaired glycosylation processing and aberrant membrane trafficking of PC-1 was observed in AQP11 KO mice, suggesting the involvement of AQP11 in proper glycosylation of PC-1 in ER.

Research Products

• [Journal Article] Immunolocalization and translocation of aquaporin-5 water channel in sweat glands (2013)
  • Author(s): Inoue R, Sohara E, Rai T, Satoh T, Yokozeki H, Sasaki S, Uchida S.
  • Journal Title: J Dermatol Sci Volume: 70 Pages: 26-33
  • Peer Reviewed
• [Journal Article] Development of enzyme-linked immunosorbent assays for urinary thiazide-sensitive Na-Cl cotransporter (NCC) measurement (2013)
  • Author(s): Isobe K, Mori T, Asano T, Kawaguchi H, Nonoyama S, Kumagai N, Kamada F, Morimoto T, Hayashi M, Sohara E, Rai T, Sasaki S, Uchida S.
  • Journal Title: Am J Physiol Renal Physiol Volume: 305 Pages: F1374-81
  • Peer Reviewed
• [Journal Article] Chemical library screening for WNK signalling inhibitors using fluorescence correlation spectroscopy (2013)
  • Author(s): Mori T, Kikuchi E, Watanabe Y, Fujii S, Ishigami-Yuasa M, Kagechika H, Sohara E, Rai T, Sasaki S, Uchida S.
  • Journal Title: Biochem J Volume: 455 Pages: 339-45
  • Peer Reviewed
• [Journal Article] Decrease of WNK4 ubiquitination by disease-causing mutations of KLHL3 through different molecular mechanisms (2013)
  • Author(s): Mori Y, Wakabayashi M, Mori T, Araki Y, Sohara E, Rai T, Sasaki S, Uchida S.
  • Journal Title: Biochem Biophys Res Commun Volume: 439 Pages: 30-4
  • Peer Reviewed
• [Journal Article] Treatment with 17-allylamino-17-demethoxygeldanamycin ameliorated symptoms of Bartter syndrome type caused by mutated Bsnd in mice (2013)
  • Author(s): Nomura N, Kamiya K, Ikeda K, Yui N, Chiga M, Sohara E, Rai T, Sasaki S, Uchida S.
  • Journal Title: Biochem Biophys Res Commun Volume: 441 Pages: 544-49
  • Peer Reviewed
• [Journal Article] Hereditary nephrogenic diabetes insipidus in Japanese patients : analysis of 78 families and report of 22 new mutations in AVPR2 and AQP2 (2013)
  • Author(s): Sasaki S, Chiga M, Kikuchi E, Rai T, Uchida S.
  • Journal Title: Clin Exp Nephrol Volume: 17 Pages: 338-344
  • Peer Reviewed
• [Journal Article] KLHL2 interacts with and ubiquitinates WNK kinases (2013)
  • Author(s): Takahashi D, Mori T, Wakabayashi M, Mori Y, Susa K, Zeniya M, Sohara E, Rai T, Sasaki S, Uchida S.
  • Journal Title: Biochem Biophys Res Commun Volume: 437 Pages: 457-62
  • Peer Reviewed
• [Journal Article] Impaired KLHL3-mediated ubiquitination of WNK4 causes human hypertension (2013)
  • Author(s): Wakabayashi M, Mori T, Isobe K, Sohara E, Susa K, Araki Y, Chiga M, Kikuchi E, Nomura N, Mori Y, Matsuo H, Murata T, Nomura S, Asano T, Kawaguchi H, Nonoyama S, Rai T, Sasaki S, Uchida S.
  • Journal Title: Cell Rep Volume: 3 Pages: 858-68
  • Peer Reviewed
• [Journal Article] Dietary salt intake regulates WNK3-SPAK-NKCC1 phosphorylation cascade in mouse aorta through angiotensin II (2013)
  • Author(s): Zeniya M, Sohara E, Kita S, Iwamoto T, Susa K, Mori T, Oi K, Chiga M, Takahashi D, Yang SS, Lin SH, Rai T, Sasaki S, Uchida S.
  • Journal Title: Hypertension Volume: 62 Pages: 872-878
  • Peer Reviewed
• [Journal Article] Phosphorylation of Na-Cl cotransporter by OSR1 and SPAK kinases regulates its ubiquitination (2012)
  • Author(s): Hossain Khan MZ, Sohara E, Ohta A, Chiga M, Inoue Y, Isobe K, Wakabayashi M, Oi K, Rai T, Sasaki S, Uchida S.
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 425 Pages: 456-61
  • Peer Reviewed
• [Journal Article] Phosphatidylinositol 3-kinase/Akt signaling pathway activates the WNK-OSR1/SPAK-NCC phosphorylation cascade in hyperinsulinemic db/db mice (2012)
  • Author(s): Nishida H, Sohara E, Nomura N, Chiga M, Alessi DR, Rai T, Sasaki S, Uchida S.
  • Journal Title: Hypertension Volume: 60 Pages: 981-90
  • Peer Reviewed
• [Journal Article] A minor role of WNK3 in regulating phosphorylation of renal NKCC2 and NCC co-transporters in vivo (2012)
  • Author(s): Oi K, Sohara E, Rai T, Misawa M, Chiga M, Alessi DR, Sasaki S, Uchida S.
  • Journal Title: Biol.Open Volume: 1 Pages: 120-7
  • Peer Reviewed
• [Journal Article] Effect of heterozygous deletion of WNK1 on the WNK-OSR1/ SPAK-NCC/NKCC1/NKCC2 signal cascade in the kidney and blood vessels (2012)
  • Author(s): Susa K, Kita S, Iwamoto T, Yang SS, Lin SH, Ohta A, Sohara E, Rai T, Sasaki S, Alessi DR, Uchida S.
  • Journal Title: Clin Exp. Nephrol Volume: 16 Pages: 530-8
  • Peer Reviewed
• [Journal Article] WNK-OSR1/SPAK-NCC signal cascade has circadian rhythm dependent on aldosterone (2012)
  • Author(s): Susa K, Sohara E, Isobe K, Chiga M, Rai T, Sasaki S, Uchida S.
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 427 Pages: 743-7
  • Peer Reviewed
• [Journal Article] Does aβ2-adrenergic receptor-WNK4-Na-Cl co-transporter signal cascade exist in the in vivo kidney? (2012)
  • Author(s): Uchida S, Chiga M, Sohara E, Rai T, Sasaki S.
  • Journal Title: Nat. Med Volume: 18 Pages: 1324-5
  • Peer Reviewed
• [Presentation] Analyses of KLHL3 mutants that cause Pseudohypoaldosteronism type II (2013)
  • Author(s): Mori Y, Wakabayashi M, Mori T, Araki Y, Sohara E, Rai T, Sasaki S, Uchida S.
  • Organizer: The 46^<th> Annual Meeting of American Society of Nephrology
  • Place of Presentation: Atlanta
  • Year and Date: 2013-11-09
• [Presentation] KLHL2 interacts with and ubiquitinates WNK kinases (2013)
  • Author(s): Takahashi D, Mori T, Wakabayashi M, Mori Y, Susa K, Zeniya M, Sohara E, Rai T, Sasaki S, Uchida S.
  • Organizer: The 46^<th> Annual Meeting of American Society of Nephrology
  • Place of Presentation: Atlanta
  • Year and Date: 2013-11-09
• [Presentation] Impaired KLHL3-mediated ubiquitination of WNK4 activates OSR1 and SPAK kinases-NaCl cotransporter (NCC) signaling and causes hypertension (2013)
  • Author(s): Wakabayashi M, Mori T, Isobe K, Sohara E, Susa K, Araki Y, Chiga M, Kikuchi E, Nomura N, Mori Y, Rai T, Sasaki S, Uchida S.
  • Organizer: The 46^<th> Annual Meeting of American Society of Nephrology
  • Place of Presentation: Atlanta
  • Year and Date: 2013-11-09
• [Presentation] WNK3 Regulates Blood Pressure Through the Regulation of Vascular OSR1/SPAK-NKCC1 Phosphorylation Cascade (2013)
  • Author(s): Zeniya M, Sohara E, Kita S, Iwamoto T, Susa K, Mori T, Oi K, Chiga M, Takahashi D, Yang SS, Lin SH, Rai T, Sasaki S, Uchida S.
  • Organizer: The 46^<th> Annual Meeting of American Society of Nephrology
  • Place of Presentation: Atlanta
  • Year and Date: 2013-11-09
• [Presentation] Aberrant Glycosylation and Localization of Polycystin-1 Cause Polycystic Kidney in AQP11-Knockout Mice (2013)
  • Author(s): Inoue Y, Sohara E, Kobayashi K, Rai T, Ishibashi K, Horie S, Su X, Zhou J, Sasaki S, Uchida S.
  • Organizer: The 46^<th> Annual Meeting of American Society of Nephrology
  • Place of Presentation: Atlanta
  • Year and Date: 2013-11-07
• [Presentation] Clinical Significance of Urinary Thiazide-Sensitive Na-Cl Cotransporter (NCC) Measurement by Newly Development Enzyme-Linked Immunosorbent Assays (2013)
  • Author(s): Isobe K, Mori T, Sohara E, Rai T, Sasaki S, Uchida S.
  • Organizer: The 46^<th> Annual meeting of American Society of Nephrology
  • Place of Presentation: Atlanta
  • Year and Date: 2013-11-07
• [Presentation] Chemical library screening for WNK signaling inhibitors by using fluorescent correlation spectroscopy (2013)
  • Author(s): Mori T, Eriko K, Sohara E, Rai T, Sasaki S, Uchida S.
  • Organizer: The 46^<th> Annual Meeting of American Society of Nephrology
  • Place of Presentation: Atlanta
  • Year and Date: 2013-11-07
• [Presentation] Low salt intake decreased transcription and protein level of KLHL3 in mouse kidney (2013)
  • Author(s): Susa K, Sohara E, Zeniya M, Rai T, Sasaki S, Uchida S.
  • Organizer: The 46^<th> Annual Meeting of American Society of Nephrology
  • Place of Presentation: Atlanta
  • Year and Date: 2013-11-07
• [Presentation] Ser-261 phosphorylation is an endocytic signal of aquaporin-2 water channel (2013)
  • Author(s): Yui N, Uchida S, Sasaki S.
  • Organizer: The 46^<th> Annual Meeting of American Society of Nephrology
  • Place of Presentation: Atlanta
  • Year and Date: 2013-11-07
• [Presentation] Hereditary nephrogenic diabetes insipidus (NDI) in Japanese patients : Analysis of 73 families (2012)
  • Author(s): Sasaki S, Chiga M, Kikuchi E, Uchida S.
  • Organizer: The 45th Annual Meeting of American Society of Nephrology
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2012-11-02
• [Presentation] WNK4-OSR1/SPAK-NCC signal cascade has circadian rhythm dependent on aldosterone (2012)
  • Author(s): Susa K, Sohara E, Isobe K, Chiga M, Rai T, Sasaki S, Uchida S.
  • Organizer: The 45th Annual Meeting of American Society of Nephrology
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2012-11-02
• [Presentation] Chemical library screening for direct SPAK inhibitors by a newly developed ELISA system (2012)
  • Author(s): Kikuchi E, Mori T, Isobe K, Sohara E, Rai T, Sasaki S, Uchida S.
  • Organizer: The 45th Annual Meeting of American Society of Nephrology
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2012-11-01
• [Presentation] Generation and analysis of WT-WNK4 transgenic mice revealed the physiological role of WNK4 (2012)
  • Author(s): Mori T, Sohara E, Rai T, Sasaki S, Uchida S.
  • Organizer: The 45th Annual Meeting of American Society of Nephrology
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2012-11-01
• [Remarks] 東京医科歯科大学腎臓内科学ホームページ
  • URL: http://www.tmd.ac.jp/grad/kid/kid-J.htm