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Studies on gating and permission mechanisms for maturation of secretory cargo proteins

Research Project

Project/Area Number 19370044
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Structural biochemistry
Research InstitutionFukushima Medical University

Principal Investigator

WADA Ikuo  Fukushima Medical University, 医学部, 教授 (40182969)

Co-Investigator(Kenkyū-buntansha) HATSUZAWA Kiyotaka  福島県立医科大学, 医学部, 准教授 研究者 (20256655)
HASHIMOTO Hitoshi  福島県立医科大学, 医学部, 助教 (50372826)
Co-Investigator(Renkei-kenkyūsha) NAKANISHI Hideki  福県立医科大学, 医学部, 助教 (30457783)
HIGASHI Tsunehito  福県立医科大学, 医学部, 助教 (90453018)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2008: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Fiscal Year 2007: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Keywords細胞小器官 / ダイナミクス / 一分子トラッキング / 糖鎖 / 分泌系 / 小胞体 / 1分子動態 / 品質管理 / 分子イメージング / フォールディング / 1分子イメージング / 蛍光相関分光法 / 全反射顕微鏡
Research Abstract

To understand why mammalian cells are capable of producing secreted proteins of high quality in a highly coordinated manner, we have developed a system to examine single molecular dynamics of cargo proteins in the endoplasmic reticulum. Series of analyses have indicated that lumen of the ER are equipped with a machinery that restricts simple diffusion of cargo proteins through a grip of N-linked oligosaccharides using actin cytoskeleton. Since this regulation becomes most prominent at higher temperature, we propose that this constitutes a basic machinery for cargo maturation.

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (42 results)

All 2009 2008 2007 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (25 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Sec22b Is a Negative Regulator of Phagocytosis in Macrophages.2009

    • Author(s)
      Hatsuzawa K, Hashimoto H, Hashimoto H, Arai S, Tamura T, Higa-Nishiyama A, Wada I.
    • Journal Title

      Mol Biol Cell 20(20)

      Pages: 4435-4443

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of Na+/Ca2+ exchanger in migration and contraction of cultured rat tendon fibroblasts.2009

    • Author(s)
      Sakamoto K, Owada Y, Shikama Y, Wada I, Waguri S, Iwamoto T, Kimura J.
    • Journal Title

      J Physiol 587(22)

      Pages: 5345-5359

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sec22b Is a Negative Regulator of Phagocytosis in Macrophages2009

    • Author(s)
      Hatsuzawa K., et al
    • Journal Title

      Mol Biol Cell 20

      Pages: 4435-4443

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Rab GTPase Ypt11 functions in bud-directed transport of the Golgi by linking Myo2 to the coatomer subunit Ret2.2008

    • Author(s)
      Arai S, Noda Y, Kainuma S, Wada I, Yoda K.
    • Journal Title

      Current Biology 18(13)

      Pages: 987-991

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Human XTP3-B forms an ER quality-control scaffold with the Hrd1-Sel1l ubiquitin ligase complex and BiP.2008

    • Author(s)
      Hosokawa N, Wada I, Nagasawa K, Moriyama T, Okawa K, Nagata K
    • Journal Title

      J Biol Chem 283(30)

      Pages: 20914-20924

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulated motion of glycoproteins revealed by direct visualization of a single cargo in the endoplasmic reticulum.2008

    • Author(s)
      Nagaya H, Tamura T, Higa-Nishiyama A, Ohashi T, Takeuchi M, Hashimoto H, Hatsuzawa K, Kinjo M, Okada T, Wada I.
    • Journal Title

      J Cell Biol 180(1)

      Pages: 129-143

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] The Rab GTPase Ypt11 functions in bud-directed transport of the Golgi by linking Myo2 to the coatomer subunit Ret22008

    • Author(s)
      Arai S., et al
    • Journal Title

      Current Biology 18

      Pages: 987-991

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human XTP3-B forms an ER quality-control scaffold with the Hrd1-Sell1 ubiquitin lipase complex and BiP2008

    • Author(s)
      Hosokawa N., et al
    • Journal Title

      J Biol Chem 283

      Pages: 20914-20924

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulated motion of glycoproteins revealed by direct visualization of a single cargo in the endoplasmic reticulum2008

    • Author(s)
      Nagaya, et al.
    • Journal Title

      J Cell Biol 180

      Pages: 129-143

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulated motion of glycoproteins revealed by direct visualization of a single cargo in the endoplasmic reticulum2008

    • Author(s)
      Nagaya H, et al.
    • Journal Title

      J Cell Biol 180

      Pages: 129-143

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Meltrin beta/ADAM19 Mediates Ectodomain Shedding of Neuregulin beta1 in the Golgi Apparatus: Fluorescence Correlation Spectroscopic Observation of the Dynamics of Ectodomain Shedding in Living Cells.2007

    • Author(s)
      Yokozeki T, Wakatsuki S, Hatsuzawa K, Black RA, Wada I, Sehara-Fujisawa A.
    • Journal Title

      Genes to Cells 12(3)

      Pages: 329-343

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Carboxyl-Terminal Disulfide Bond of Acid Sphingomyelinase Is Critical for Its Secretion and Enzymatic Function.2007

    • Author(s)
      Lee C-Yin, Tamura T, Rabah N, Lee D-Y, Ruel I, Hafiane A, Iatan I, Nyholt D, Laporte F, Lazure C, Wada I, Krimbou L, Genest J.
    • Journal Title

      Biochemistry 46(51)

      Pages: 14969-14978

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Carboxyl-Terminal Disulfide Bond of Acid Sphingomyelinase Is Critical for Its Secretion and Enzymatic Function2007

    • Author(s)
      Lee, C-Yin, et al.
    • Journal Title

      Biochemistry 46

      Pages: 14969-14978

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Meltrin beta/ADAM19 Mediates Ectodomain Shedding of Neuregulin betal in the Golgi Apparatus:Fluorescence Correlation Spectroscopic Observation of the Dynamics of Ectodomain Shedding in Living Cells2007

    • Author(s)
      Yokozeki T, et al.
    • Journal Title

      Genes to Cells 12

      Pages: 329-343

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Jump distance analysis によるアスパラギン結合糖鎖を持つカーゴ動態の解析2009

    • Author(s)
      和田郁夫、東恒仁、田中学
    • Organizer
      第82回日本生化学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2009-10-22
    • Related Report
      2008 Annual Research Report
  • [Presentation] Probing the environment of the endoplasmic reticulum lumen by analyzing jump distance of a cargo protein.2009

    • Author(s)
      Arai S, Higashi T, Tanaka G, Wada I.
    • Organizer
      4th Cell Stress Society International (CSSI) Congress on Stress Responses in Biology and Medicine
    • Place of Presentation
      Sapporo
    • Year and Date
      2009-10-08
    • Related Report
      2008 Final Research Report
  • [Presentation] Probing the environment of the endoplasmic reticulum lumen by analyzing jump distance of a cargo protein2009

    • Author(s)
      Saisuke Arai, Tsunehito Higashi, Gaku Tanaka, Ikuo Wada
    • Organizer
      4th Cell Stress Society International(CSSI)Congress on Stress Responses in Biology and Medicine
    • Place of Presentation
      札幌
    • Year and Date
      2009-10-08
    • Related Report
      2008 Annual Research Report
  • [Presentation] DCP1のP-bodyへの局在にはそのC末端領域が必要である2009

    • Author(s)
      東恒仁、和田郁夫
    • Organizer
      第22回日本動物細胞工学会大会
    • Place of Presentation
      筑波
    • Year and Date
      2009-07-25
    • Related Report
      2008 Final Research Report
  • [Presentation] DCP1のP-body への局在にはそのC末端領域が必要である2009

    • Author(s)
      東恒仁、和田郁夫
    • Organizer
      第22回日本動物細胞工学会大会
    • Place of Presentation
      東京
    • Year and Date
      2009-07-25
    • Related Report
      2008 Annual Research Report
  • [Presentation] SNAP-23はマクロファージのファゴソーム成熟過程に機能する2009

    • Author(s)
      櫻井千恵, 初沢清隆, 和田郁夫
    • Organizer
      第61回日本細胞生物学会大会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-06-02
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] 小胞体内における1分子ダイナミクス解析2009

    • Author(s)
      和田郁夫
    • Organizer
      第9回日本蛋白質科学会年会
    • Place of Presentation
      熊本
    • Year and Date
      2009-05-20
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] Role of Dcp1 in the formation of P-bodies.2009

    • Author(s)
      Higashi T, Wada, I.
    • Organizer
      Biophysical Society 53rd Anneal Meeting
    • Year and Date
      2009-03-04
    • Related Report
      2008 Final Research Report
  • [Presentation] Role of Dcp1 in the formation of P-bodies2009

    • Author(s)
      Tsunehito Higashi, Ikuo Wada
    • Organizer
      Biophysical Society 53rd Anneal Meeting
    • Place of Presentation
      Long Beach(CA)
    • Year and Date
      2009-03-04
    • Related Report
      2008 Annual Research Report
  • [Presentation] 出芽酵母におけるゴルジ体インヘリタンスの分子機構2008

    • Author(s)
      荒井斉祐野田陽一和田郁夫依田幸司
    • Organizer
      第31回日本分子生物学会年会第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-12
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] J774 Macrophages Overexpressing LRG-47, an IFN-γ-inducible p47 GTPase, Are Deficient in Phagocytosis2008

    • Author(s)
      初沢清隆, 櫻井千恵, 橋本裕美, 和田郁夫
    • Organizer
      第31回日本分子生物学会年会第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-12
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] P-body形成におけるDCP1の役割2008

    • Author(s)
      東恒仁, 和田郁夫
    • Organizer
      第31回日本分子生物学会年会第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-12
    • Related Report
      2008 Final Research Report
  • [Presentation] P-body 形成におけるDCP1の役割2008

    • Author(s)
      東恒仁、和田郁夫
    • Organizer
      第31回日本分子生物学会年会第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-12
    • Related Report
      2008 Annual Research Report
  • [Presentation] 新規レクチンによる小胞体タンパク質品質管理機構2008

    • Author(s)
      細川暢子和田郁夫長澤孝治森山達哉大川克也永田和宏
    • Organizer
      第31回日本分子生物学会年会第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-09
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] Regulated motion of cargo proteins in the endoplasmic reticulum as revealed by single molecule techniques.2008

    • Author(s)
      Higashi Y, Nagaya H, Tanaka G, Abe M, Wada I.
    • Organizer
      Joint Meeting of the Biophysical Society 52nd Anneal Meeting & 16th International Biophysics Congress
    • Place of Presentation
      LongBeach, CA
    • Year and Date
      2008-02-06
    • Related Report
      2008 Final Research Report
  • [Presentation] Regulated motion of cargo proteins in the endoplasmic reticulum as revealed by single molecule techniques2008

    • Author(s)
      Higashi T, et al.
    • Organizer
      Joint Meeting of the Biophysical Society 52nd Anneal Meeting & 16th International Biophysics Congress
    • Place of Presentation
      Longbeach, LA, USA
    • Year and Date
      2008-02-06
    • Related Report
      2007 Annual Research Report
  • [Presentation] 小胞体由来Russell body様構造体の形成機構:変異型アンチトロンビンを用いた解析2007

    • Author(s)
      木村耕士, 上田由美子, 和田郁夫, 今中恒雄
    • Organizer
      第30回日本分子生物学会年会第80回日本生化学会大会合同大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-13
    • Related Report
      2008 Final Research Report
  • [Presentation] 変異型アンチトロンビンにより形成されるRussell bodyの細胞内動態2007

    • Author(s)
      Ohkubo, et al.
    • Organizer
      第30回日本分子生物学会年会第80回日本生化学会大会合同大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] Sec22b, an ER-localized SNARE protein, is a negative regulator of the ER-mediated phagocytosis2007

    • Author(s)
      Hatuszawa, et al.
    • Organizer
      第30回日本分子生物学会年会第80回日本生化学会大会合同大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] p24 works in the process of cargo pachaging2007

    • Author(s)
      Hashimoto, et al.
    • Organizer
      第30回日本分子生物学会年会第80回日本生化学会大会合同大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] p24 works in the process of cargo pachaging.2007

    • Author(s)
      橋本仁志、和田郁夫、Nilsson T.
    • Organizer
      第30回日本分子生物学会年会第80回日本生化学会大会合同大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-12
    • Related Report
      2008 Final Research Report
  • [Presentation] Sec22b, an ER-localized SNARE protein, is a negative regulator of the ER-mediated phagocytosis.2007

    • Author(s)
      初沢清隆, 橋本裕美, 和田郁夫
    • Organizer
      第30回日本分子生物学会年会第80回日本生化学会大会合同大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-12
    • Related Report
      2008 Final Research Report
  • [Presentation] 小胞体内におけるカーゴ蛋白質1分子ダイナミクスの解析2007

    • Author(s)
      東恒仁, 中西秀樹, 大橋功一, 和田郁夫
    • Organizer
      第30回日本分子生物学会年会第80回日本生化学会大会合同大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-12
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] REGULATED DYNAMICS OF CARGO PROTEINS IN THE ENDOPLASMIC RETICULUM AS REVEALED BY SINGLE MOLECULE TECHNIQUES2007

    • Author(s)
      Wada Ikuo, et al.
    • Organizer
      10th Workshop on FCS and Related Methods
    • Place of Presentation
      札幌
    • Year and Date
      2007-11-28
    • Related Report
      2007 Annual Research Report
  • [Presentation] Regulated dynamics of cargo proteins in the endoplasmic reticulum as revealed by single molecule techniques.2007

    • Author(s)
      Wada, I.
    • Organizer
      10th Workshop on FCS and Related Methods. Sapporo.
    • Year and Date
      2007-10-08
    • Related Report
      2008 Final Research Report
  • [Book] 生細胞蛍光イメージングー阪大・北大顕微鏡コースブック2007

    • Author(s)
      木村宏・和田郁夫
    • Publisher
      共立出版
    • Related Report
      2008 Final Research Report
  • [Book] 生細胞蛍光イメージングー阪大・北大 顕微鏡コースブック2007

    • Author(s)
      木村宏、和田郁夫
    • Total Pages
      28
    • Publisher
      共立出版
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.fmu.ac.jp/home/cellsci/gyoseki.html

    • Related Report
      2008 Annual Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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