The physiological function of V-ATPase and its pathological relationships

2013 Fiscal Year Final Research Report

• Project/Area Number: 23570178
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Doshisha Women's College of Liberal Arts
• Principal Investigator: SUN-WADA Ge-Hong (孫 戈虹) 同志社女子大学, 薬学部, 教授 (00314427)
• Project Period (FY): 2011 – 2013
• Keywords: 膜輸送と輸送タンパク質 / プロトンポンプ

Research Abstract

The V-ATPases are a family of multi-subunit ATP-dependent proton pumps involved in diverse cellular processes, including acid/base homeostasis, receptor-mediated endocytosis, processing of proteins and signaling molecules, targeting of lysosomal enzymes, and activation of various degradation enzymes. These fundamental cellular activities are naturally related to higher order physiological functions in multicellular organisms. V-ATPases are involved in several physiological processes, including renal acidification, bone resorption, and neurotransmitter accumulation. We have shown that the Full-length ATP6ap2 is essential for the assembly of V-ATPase. We also we have identified 2 different populations of mature osteoclasts in situ, corresponding with the static – bone resorptive (R) and moving – nonresorptive (N) fractions, with the transition between these states critically controlled by RANKL and showing a strong correlation to the state of cell motility.

Research Products

• [Journal Article] Positive and negative regulation of developmental signaling by the endocytic pathway (2013)
  • Author(s): Wada, Y. and Sun-Wada, G. H.
  • Journal Title: Curr. Opin. Genet. Dev. Volume: (in press)
  • Peer Reviewed
• [Journal Article] The role of individual domains and the significance of shedding of ATP6AP2/ (pro)renin receptor in vacuolar H+-ATPase biogenesis (2013)
  • Author(s): Kinouchi, K., Ichihara, A., Sano, M., Sun-Wada, G.H., Wada, Y., Ochi, H., Fukuda, T., and Itoh, H.
  • Journal Title: PLos One Volume: 78603
  • Peer Reviewed
• [Journal Article] Vacuolar proton pump (V-ATPase) and insulin secretion (2013)
  • Author(s): Sun-Wada, G.H., Wada, Y. in "H+-ATPase activated by glucose; a possible link to diabetic complications", Nakamura, S. ed.
  • Journal Title: Pan Stanford Publishing Pte Ltd., Singapore Volume: (in press)
• [Journal Article] Vacuolar-type proton pump ATPases : Acidification and pathological relationships (2013)
  • Author(s): Sun-Wada, G. H., and Wada, Y.
  • Journal Title: Histol. Histopathol Volume: 28 Pages: 805-815
  • Peer Reviewed
• [Journal Article] Microautophagy in the visceral endoderm is essential for mouse early development (2013)
  • Author(s): Wada, Y., Sun-Wada, G. H., and Kawamura, N.
  • Journal Title: Autophagy Volume: 9 Pages: 252-254
• [Journal Article] Critical roles of the PtdIns(3,5)P2-producing enzyme phosphatidylinositol phosphate kinase III in embryogenesis and intestinal homeostasis (2013)
  • Author(s): Takasuga, S., Horie, Y., Sasaki, J., Sun-Wada, G. H., Kawamura, N., Iizuka, R., Kontani, K., Harada, A., Katada, T., Suzuki, A., Wada, Y., Ohnishi, H., and Sasaki, T.
  • Journal Title: Proc. Natl. Acad. Sci. USA. Volume: 110 Pages: 1726-1731
  • Peer Reviewed
• [Journal Article] Dynamic visualization of RANKL and Th17-mediated control of osteoclast function (2013)
  • Author(s): Kikuta, J., Wada, Y., Kowade, T., Wang, Z., Sun-Wada, G. H., Nishiyama, I., Mizukami, S., Maiya, N., Yasuda, H., Kumanogoh, A., Kikuchi, K., Germain, R., and Ishii, M. J . Clin.
  • Journal Title: Invest Volume: 123 Pages: 866-873
  • Peer Reviewed
• [Journal Article] mVam2 依存性エンドサイトーシスによるマウス胚発生におけるBMP(bone morphogenetic protein)シグナルの制御 (2013)
  • Author(s): 和田戈虹, 和田洋
  • Journal Title: 生化学 Volume: 85 Pages: 806-809
• [Journal Article] elivery of endosomes to lysosomes via microautophagy in the visceral endoderm of mouse embryos.(Selected as the Journal's image of the issue) (2012)
  • Author(s): Kawamura, N., Sun-Wada, G. H., Aoyama, M., Harada, A., Takasuga, S., Sasaki, T., and Wada, Y.
  • Journal Title: Nat. Commun. Volume: 3 Pages: 1071
  • Peer Reviewed
• [Journal Article] SNAP-23regulates phagosome formation and maturation in macrophages (2012)
  • Author(s): Sakurai, S., Hashimoto, H., Nakanishi, H., Arai, S., Wada, Y., Sun-Wada, G-H, Wada, I., Hatsuzawa, K.
  • Journal Title: Mol. Biol. Cell Volume: 23 Pages: 4849-4863
  • Peer Reviewed
• [Journal Article] Spatial restriction of bone morphogenetic protein signaling in mouse gastrula through the mVam2-dependent endocytic pathway(§Equal contribution.) (2012)
  • Author(s): §Aoyama, M., §Sun-Wada, G. H., Yamamoto, A., Yamamoto, M., Hamada, H., and Wada, Y.
  • Journal Title: Dev. Cell Volume: 22 Pages: 1173-1175
  • Peer Reviewed
• [Journal Article] マウスの初期胚におけるBMP シグナルのパターンはVam2 に依存するエンドサイトーシス経路により制御されている (2012)
  • Author(s): 和田戈虹, 和田 洋
  • Journal Title: ライフサイエンス新着論文レヴユー 科学技術振興機構バイオサイエンスデーターベースセンター
• [Journal Article] (Pro)renin receptor is essential for normal podocyte structure and function (2011)
  • Author(s): Oshima, Y., Kinouchi, K., Ichihara, A., Sakoda, M., Kurauchi-Mito, A., Bokuda, K., Narita, T., Kurosawa, H., Sun-Wada, G. H., Wada, Y., Yamada, T., Takemoto, M., Saleem, M. A., Quaggin, S. E., Itoh, H. J .
  • Journal Title: Am. Soc. Nephrol. Volume: 22 Pages: 2203-2212
  • Peer Reviewed
• [Journal Article] (Pro)renin Receptor is Essential for Expression of Slit Diaphragm Proteins in Murine Podocytes (2011)
  • Author(s): Kinouchi, K; Ichihara, A; Oshima, Y; Kurauchi-Mito, A; Kurosawa, H; Sun-Wada, G.H; Wada, Y; Yamada, T; Takemoto, M; Saleem, MA; Quaggin, SE; Itoh, H.
  • Journal Title: Hypertension Volume: 58 Pages: 55-56
  • Peer Reviewed
• [Journal Article] The a3 isoform vacuolar type H+-ATPase promotes distant metastasis in the mouse B16 melanoma cells (2011)
  • Author(s): Nishisho, T., Hata, K., Nakanishi, M., Morita, Y., Sun-Wada, G. H., Wada, Y., Yasui, N., and Yoneda, T.
  • Journal Title: Mol. Cancer Res. Volume: 9 Pages: 844-855
  • Peer Reviewed
• [Journal Article] Vacuolar H+-ATPase subunit Voa1 and Voa2 cooperatively regulate secretory vesicle acidification, transmitter uptake and storage (2011)
  • Author(s): Saw, N. M., Kang, S. Y., Parsaud, L., Han, G. A., Jiang, T., Grzegorczyk, K., Surkont, M., Sun-Wada, G. H., Wada, Y., Li. L., and Sugita, S.
  • Journal Title: Mol. Biol. Cell Volume: 22 Pages: 3394-3409
  • Peer Reviewed
• [Journal Article] Generation of chicken monoclonal antibodies against the a1, a2, and a3 subunit isoforms of vacuolar-type proton ATPase (2011)
  • Author(s): Sun-Wada, G. H., Tabata, H., Kuhara, M., Kitahara, I., Takashima, Y., and Wada, Y.
  • Journal Title: Hybridoma Volume: 30 Pages: 199-203
  • Peer Reviewed
• [Presentation] Unique endocytic pathway in early mouse embryos and its implication in signal regulation The 61st NIBB Conference (2013)
  • Author(s): Wada Y and Sun-Wada, G. H.
  • Organizer: Cellular Community in Mammalian Embryogenesis
  • Place of Presentation: Okazaki, Japan
  • Year and Date: 20130710-12
• [Presentation] hysiological functions of subunit isoform a3 of proton pump V-ATPase Cold Spring Harbor Asia Conference (2013)
  • Author(s): P Wada Y and Sun-Wada, G. H.
  • Organizer: Membrane Protein Structure & Function
  • Place of Presentation: 蘇州、中国
  • Year and Date: 20130500
• [Presentation] Microautophagic assembly of large vacuoles in mammalian embryonic tissues Cold Spring Harbor Asia Conference (2013)
  • Author(s): Wada Y and Sun-Wada, G. H.
  • Organizer: Membrane Protein Structure & Function
  • Place of Presentation: 蘇州、中国
  • Year and Date: 20130500
• [Presentation] Rab7-dependent microautophagy in the visceral endoderm is essential for mouse early development (2013)
  • Author(s): Wada Y and Sun-Wada, G. H.
  • Organizer: EXPERIMENTAL BIOLOGY 2013
  • Place of Presentation: Boston, USA
  • Year and Date: 20130400
• [Presentation] プロトンポンプV-ATPase aサブユニットアイソフォームのマウス初期胚における発現 (2013)
  • Author(s): 山中加也, 和田戈虹, 他.
  • Organizer: 第63回日本薬学会近畿支部総会・大会
  • Place of Presentation: 同志社女子大学
  • Year and Date: 2013-10-12
• [Presentation] プロトンポンプV-ATPase G2アイソフォーム遺伝子欠損マウスの作製とその表現型 (2013)
  • Author(s): 殿村真優, 和田戈虹, 他.
  • Organizer: 第63回日本薬学会近畿支部総会・大会
  • Place of Presentation: 同志社女子大学
  • Year and Date: 2013-10-12
• [Presentation] リソソーム膜輸送におけるmVam2および低分子GTPase Arl8bとrab7の役割 (2013)
  • Author(s): 信貴美里, 和田戈虹, 他.
  • Organizer: 第63回日本薬学会近畿支部総会・大会
  • Place of Presentation: 同志社女子大学
  • Year and Date: 2013-10-12
• [Presentation] マウス低分子量GTPase Rab7の初期胚発生における機能解析 (2013)
  • Author(s): 川村暢幸, 和田戈虹, 他.
  • Organizer: 第63回日本薬学会近畿支部総会・大会
  • Place of Presentation: 同志社女子大学
  • Year and Date: 2013-10-12
• [Presentation] THE STRUCTURAL ANALYSIS OF (PRO)RENIN RECEPTOR IN VACUOLAR H+-ATPase ASSEMBLY (2013)
  • Author(s): Wada Y and Sun-Wada, G. H
  • Organizer: The World Conference of Nephrology 2013
  • Place of Presentation: Hong Kong
  • Year and Date: 2013-06-02
• [Presentation] Physiological functions of subunit isoforms of proton pump V-ATPase FAOBMB (2013)
  • Author(s): Sun-Wada, G. H.
  • Organizer: mini-symposium
  • Place of Presentation: Iwate Medical university
  • Year and Date: 2013-04-05
• [Presentation] マウス初期胚におけるミクロオートファジーの解析 (2012)
  • Author(s): 川村暢幸, 和田戈虹, 他.
  • Organizer: 第62回日本薬学会近畿支部総会・大会
  • Place of Presentation: 武庫川女子大学
  • Year and Date: 20121000
• [Presentation] マウス初期胚BMPシグナル制御におけるmVam2の役割 (2012)
  • Author(s): 宮崎宏美, 和田戈虹, 他.
  • Organizer: 第62回日本薬学会近畿支部総会・大会
  • Place of Presentation: 武庫川女子大学
  • Year and Date: 20121000
• [Presentation] マウス低分子量GTPase Rab7の機能解析(I)–細胞における変異表現型 (2012)
  • Author(s): 古川阿弓, 和田戈虹, 他.
  • Organizer: 第62回日本薬学会近畿支部総会・大会
  • Place of Presentation: 武庫川女子大学
  • Year and Date: 20121000
• [Presentation] マウス低分子量GTPase Rab7の機能解析(II)–初期発生の異常 (2012)
  • Author(s): 稲葉佳南, 和田戈虹, 他.
  • Organizer: 第62回日本薬学会近畿支部総会・大会
  • Place of Presentation: 武庫川女子大学
  • Year and Date: 20121000
• [Presentation] 液胞型プロトンATPase ATP6Vocサブユニット欠損胚の解析 (2012)
  • Author(s): 石川礼、和田戈虹, 他.
  • Organizer: 第62回日本薬学会近畿支部総会・大会
  • Place of Presentation: 武庫川女子大学
  • Year and Date: 20121000
• [Presentation] Rab7-dependent microautophagy in gastrulating mouse embryo (2012)
  • Author(s): Wada Y and Sun-Wada, G. H.
  • Organizer: Cold Spring Harbor Asia Conference Shanghai
  • Place of Presentation: China
  • Year and Date: 20120900
• [Presentation] (Pro)renin Receptor is essential for filtration barrier in glomerular podocyte (2012)
  • Author(s): 和田戈虹, 他.
  • Organizer: 15th International & 14th European Congress of Endocrinology Florence
  • Place of Presentation: Italy
  • Year and Date: 20120505-09
• [Presentation] Delivery of endosome to vacuole via microautophagy in visceral endoderm of mouse embryo EMBO Workshop Lineage Commitments (2011)
  • Author(s): Wada Y and Sun-Wada, G. H.
  • Organizer: Emphasis on extraembryonic-embryonic interfaces Leuven
  • Place of Presentation: Belgium
  • Year and Date: 20111000
• [Presentation] Endocytic regulation of BMP signalling during mouse gastrulation EMBO Workshop Lineage Commitments (2011)
  • Author(s): Wada Y and Sun-Wada, G. H.
  • Organizer: Emphasis on extraembryonic-embryonic interfaces Leuven
  • Place of Presentation: Belgium
  • Year and Date: 20111000
• [Presentation] ATP6AP2/(プロ)レニン受容体はマウス腎糸球体上皮細胞の発達に必須である (2011)
  • Author(s): 和田戈虹, 他
  • Organizer: 第84回日本内分泌値学会学術総会
  • Place of Presentation: 神戸
  • Year and Date: 20110400
• [Presentation] X染色体上で調節される心筋細胞(プロ)レニン受容体の生理的機能 (2011)
  • Author(s): 和田戈虹, 他
  • Organizer: 第84回日本内分泌値学会学術総会
  • Place of Presentation: 神戸
  • Year and Date: 20110400
• [Presentation] Prorenin受容体の基礎と臨床 (2011)
  • Author(s): 和田戈虹, 他
  • Organizer: 第75回日本循環器学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20110300
• [Presentation] 細胞内酸性環境を維持する(プロ)レニン受容体の生理的な機能 (2011)
  • Author(s): 和田戈虹, 他
  • Organizer: 第40回日本心脈管作動物質学会
  • Place of Presentation: 高松
  • Year and Date: 20110200
• [Remarks]
  • URL: http://research-db.dwc.doshisha.ac.jp/rd/html/japanese/researchersHtml/2704/2704_Researcher.html