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Study for protein binding to the cholesterol-rich secretory granule membrane in neuroendocrine cells

Research Project

Project/Area Number 25440052
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Functional biochemistry
Research InstitutionAkita Prefectural University

Principal Investigator

HOSAKA Masahiro  秋田県立大学, 生物資源科学部, 教授 (80311603)

Co-Investigator(Renkei-kenkyūsha) WATANABE Tsuyoshi  旭川医科大学, 医学部, 教授 (80220903)
Bochimoto Hiroki  旭川医科大学, 医学部, 助教 (60632841)
YAMADA Keiichi  群馬大学, 工学研究院, 助教 (70323334)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords分泌顆粒 / コレステロール / グラニンタンパク質 / 内分泌細胞
Outline of Final Research Achievements

Prior to secretion, regulated peptide hormones are selectively sorted to secretory granules (SGs) at the trans-Golgi network (TGN) in endocrine cells. Secretogranin III (SgIII) appears to facilitate SG sorting process by tethering of protein aggregates containing chromogranin A (CgA) and peptide hormones to the cholesterol-rich SG membrane (SGM).
In this study, we evaluated the role of cholesterol binding protein, especially on SgIII, in SG sorting. In the SgIII-knockout mice, plasma ACTH was considerably impaired under highly stress condition. Similarly, plasma glucose level in the SgIII-knockout mice under highly stress condition were highly elevated at glucorse tolerance test. These data indicated SgIII works as sorting receptor in living animals.
Biochemical protein screening for binding to cholesterol at the SGM indicated that several candidate proteins, including granins and processing enzyme, bound directly to the SGM in a cholesterol-dependent manner.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (29 results)

All 2016 2015 2014 2013 Other

All Journal Article (11 results) (of which Peer Reviewed: 11 results,  Acknowledgement Compliant: 6 results,  Open Access: 4 results) Presentation (14 results) (of which Invited: 1 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] TORC1 activity is partially reduced under nitrogen starvation conditions in sake yeast Kyokai no. 7, Saccharomyces cerevisiae.2016

    • Author(s)
      Nakazawa N., Sato A., Hosaka M.
    • Journal Title

      J Biosci Bioeng.

      Volume: 121 Issue: 3 Pages: 247-252

    • DOI

      10.1016/j.jbiosc.2015.07.002

    • NAID

      110010051474

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Expression of Secretogranin III in Chicken Endocrine Cells: Its Relevance to the Secretory Granule Properties of Peptide Prohormone Processing and Bioactive Amine Content.2015

    • Author(s)
      Gomi H, Morikawa S, Shinmura N, Moki H, Yasui T, Tsukise A, Torii S, Watanabe T, Maeda Y, Hosaka M
    • Journal Title

      J Histochem Cytochem

      Volume: 印刷中 Issue: 5 Pages: 350-366

    • DOI

      10.1369/0022155415575032

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Intracellular and in vivo oxygen sensing using phosphorescent Ir(III) complexes with a modified acetylacetonato ligand2015

    • Author(s)
      Yoshihara T, Hosaka M, Terata M, Ichikawa K, Murayama S, Tanaka A, Mori M, Itabashi H, Takeuchi T, Tobita S.
    • Journal Title

      Anal. Chem.

      Volume: 87 Issue: 5 Pages: 2710-2717

    • DOI

      10.1021/ac5040067

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Mitochondria-targeted oxygen probes based on cationic iridium complexes with a 5-amino-1, 10-phenanthroline ligand.2015

    • Author(s)
      Yoshihara T., Murayama S., Masuda T., Kikuchi T., Yoshida K., Hosaka M., Tobita S.
    • Journal Title

      Journal of Photochemistry and Photobiology A: Chemistry

      Volume: 299 Pages: 172-182

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Silylation Improves the Photodynamic Activity of Tetraphenylporphyrin Derivatives In Vitro and In Vivo.2014

    • Author(s)
      Horiuchi H., Hosaka M, Mashio H., Terata M., Ishida S., Kyusin S., Okutsu T., Takeuchi T., Hiratsuka H.
    • Journal Title

      Chemistry

      Volume: 20 Pages: 6054-6060

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Functional Implications of the Golgi and Microtubular Network in Gonadotropes.2014

    • Author(s)
      Watanabe, T., Bochimoto, H., Koga, D., Hosaka, M., Ushiki, T.
    • Journal Title

      Mol Cell Endocrinol.

      Volume: 385 Pages: 88-96

    • NAID

      120005496543

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Functional Implications of the Golgi and Microtubular Network in Gonadotropes2014

    • Author(s)
      ②Watanabe T, Bochimoto H, Koga D, Hosaka M, Ushiki T
    • Journal Title

      Molecular and Cellular Endocrinology

      Volume: vol.385(1-2) Issue: 1-2 Pages: 88-96

    • DOI

      10.1016/j.mce.2013.10.003

    • NAID

      120005496543

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Silylation improves photodynamic activity of tetraphenylporphyrin derivative in vitro and in vivo.2014

    • Author(s)
      Horiuch H, Hosaka M, Mashio H,Ishida S, Kyushin S, Okutsu T, Takeuchi T, Hiratsuka H.
    • Journal Title

      Chemistry - A European J

      Volume: 20 Issue: 20 Pages: 1-8

    • DOI

      10.1002/chem.201303120

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intact structure of EGAM1 homeoproteins and basic amino acid residues in the common homeodomain of EGAM1 and EGAM1C contribute to their nuclear localization in mouse embryonic stem cells.2013

    • Author(s)
      Sato, S., Morita, S., Iha, M., Mori, Y., Sugawara, S., Kasuga, K., Kojima, I., Ozaki, N., Muraguchi, H., Okano, K., Iwashita, J., Murata, J., Hosaka, M., Kobayashi, M.
    • Journal Title

      J Biosci Bioeng

      Volume: S1389-1723 Issue: 2 Pages: 49-2

    • DOI

      10.1016/j.jbiosc.2013.02.007

    • NAID

      110009657192

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Chronic exercise enhances insulin secretion ability of pancreatic islets without change in insulin content in non-diabetic rats.2013

    • Author(s)
      Tsuchiya M, Manabe Y, Yamada K, Furuichi Y, Hosaka M, Fujii NL.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 11 Issue: 2 Pages: 676-682

    • DOI

      10.1016/j.bbrc.2012.11.092

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Multiple sorting systems for secretory granules ensure the regulated secretion of peptide hormones.2013

    • Author(s)
      Sun M
    • Journal Title

      Traffic

      Volume: 14 Issue: 2 Pages: 205-218

    • DOI

      10.1111/tra.12029

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 脳下垂体内分泌細胞の低酸素環境におけるACTH分泌について2015

    • Author(s)
      佐藤瑛理、前田佳紀、暮地本宙己、渡部剛、穂坂正博
    • Organizer
      第88回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] セクレトグラニンIIIが膵島インスリン生合成と分泌で果たす役割について2015

    • Author(s)
      前田佳紀、工藤咲希、暮地本宙己、村田知里、鳥居征司、渡部剛、穂坂正博
    • Organizer
      第88回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] 脳下垂体内分泌細胞の低酸素環境におけるホルモン分泌の解析2015

    • Author(s)
      佐藤瑛理、前田佳紀、暮地本宙己、渡部剛、穂坂正博
    • Organizer
      第81回日本生化学会東北支部例会
    • Place of Presentation
      仙台
    • Year and Date
      2015-05-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] セクレトグラニンIIIが生体のインスリン生合成と分泌で果たす役割2015

    • Author(s)
      前田佳紀、工藤咲希、暮地本宙己、村田知里、鳥居征司、渡部剛、穂坂正博
    • Organizer
      第81回日本生化学会東北支部例会
    • Place of Presentation
      仙台
    • Year and Date
      2015-05-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] 神経内分泌細胞の分泌顆粒に局在するセクレトグラニンIIIの生体で果たす役割2014

    • Author(s)
      前田佳紀、暮地本宙己、村田知里、鳥居征司、渡部剛、穂坂正博
    • Organizer
      第87回生化学会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Research-status Report
  • [Presentation] ;イリジウム錯体を発光プローブとする低酸素病態のイメージング:改良体の組織浸潤性と組織集積および細胞内分布について2014

    • Author(s)
      寺田幹、吉原利忠、鳥居征司、飛田成史、穂坂正博
    • Organizer
      第87回生化学会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Research-status Report
  • [Presentation] GnRHアゴニスト持続投与によりラットLH/FSH 産生細胞で生じるLH 分泌・産生機能の変化2014

    • Author(s)
      暮地本宙己、穂坂正博、板東良雄、甲賀大輔、平義樹、牛木辰男、渡部剛
    • Organizer
      日本解剖学会第60回東北・北海道連合支部学術集会
    • Place of Presentation
      福島
    • Year and Date
      2014-09-06 – 2014-09-07
    • Related Report
      2014 Research-status Report
  • [Presentation] Golgi Apparatus Structures and Function: Sorting Mechanisms of Prohormones from the Trans-Golgi Network to Secretory Granules: Concepts with Granin-Family Protein2014

    • Author(s)
      Masahiro Hosaka
    • Organizer
      Gordon Research Conferences
    • Place of Presentation
      New London, U.S.A.
    • Year and Date
      2014-07-20 – 2014-07-25
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 内分泌細胞の分泌顆粒に局在するセクレトグラニンIIIの役割2014

    • Author(s)
      前田佳紀、暮地本宙己、村田知里、鳥居征司、渡部剛、穂坂正博
    • Organizer
      第80回生化学会東北支部例会
    • Place of Presentation
      秋田
    • Year and Date
      2014-05-10
    • Related Report
      2014 Research-status Report
  • [Presentation] 生体の低酸素病態をイメージングするプローブの開発:高輝度改良体BTPDMの検証2014

    • Author(s)
      寺田幹、吉原利忠、飛田成史、穂坂正博
    • Organizer
      第80回生化学会東北支部例会
    • Place of Presentation
      秋田
    • Year and Date
      2014-05-10
    • Related Report
      2014 Research-status Report
  • [Presentation] イリジウム錯体を発光プローブとする低酸素病態のイメージング:高輝度改良体BTPDMの検証2013

    • Author(s)
      寺田幹、吉原利忠、飛田成史、穂坂正博
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Research-status Report
  • [Presentation] 分泌顆粒形成でセクレトグラニンIIIが果たす役割2013

    • Author(s)
      穂坂正博、暮地本宙己、渡部剛
    • Organizer
      第28回日本下垂体研究会
    • Place of Presentation
      花巻温泉(ホテル千秋閣:岩手)
    • Related Report
      2013 Research-status Report
  • [Presentation] Multiple sorting systems for the secretory granules ensure the regulated secretion of peptide hormones in endocrine cells2013

    • Author(s)
      Masahiro Hosaka, Hiroki Bochimoto, Tsuyoshi Watanabe
    • Organizer
      第65回日本細胞生物学会
    • Place of Presentation
      ウインクあいち(愛知県産業労働センター;名古屋))
    • Related Report
      2013 Research-status Report
  • [Presentation] 内分泌細胞の分泌顆粒形成におけるグラニンタンパク質の役割

    • Author(s)
      穂坂正博、暮地本宙己、渡部剛
    • Organizer
      第79回日本生化学会東北支部会例会
    • Place of Presentation
      東北大学(仙台)
    • Related Report
      2013 Research-status Report
  • [Remarks] 秋田県立大学 生物資源科学部 応用生物科学科 分子細胞機能研究グループ 分子生命科学分野

    • URL

      http://www.akita-pu.ac.jp/bioresource/dbt/molb/mhosaka/index.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] 分子生命科学分野(穂坂研究室)

    • URL

      http://www.akita-pu.ac.jp/bioresource/dbt/molb/mhosaka/index.html

    • Related Report
      2014 Research-status Report
  • [Remarks] 秋田県立大学 生物資源科学部 応用生物科学科 分子細胞機能研究グループ 穂坂研究室

    • URL

      http://www.akita-pu.ac.jp/bioresource/dbt/molb/mhosaka/index.html

    • Related Report
      2013 Research-status Report
  • [Patent(Industrial Property Rights)] 非アルコール性脂肪性肝炎(NASH)診断薬2016

    • Inventor(s)
      穂坂正博,畠恵司,樋渡一之,佐々木玲,高橋純一郎
    • Industrial Property Rights Holder
      穂坂正博,畠恵司,樋渡一之,佐々木玲,高橋純一郎
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-003717
    • Filing Date
      2016-01-12
    • Related Report
      2015 Annual Research Report

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Published: 2014-07-25   Modified: 2019-07-29  

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