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Molecular analysis of glaucoma-developing mechanism : Investigation of an OPTN-interacting protein

Research Project

Project/Area Number 21592223
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

OHTSUBO Masafumi  浜松医科大学, メディカルフォトニクス研究センター, 助教 (10327653)

Co-Investigator(Kenkyū-buntansha) OHISHI Kentarou  浜松医科大学, メディカルフォトニクス研究センター, 助教 (80345826)
HOSONO Katsuhiro  浜松医科大学, 医学部, 助教 (60402260)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2009: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords緑内障 / 相互作用タンパク / 遺伝子 / シグナル伝達 / 神経科学 / プロテオーム / 生体分子
Research Abstract

Among OPTN-interacting proteins, we screened those which are expressed in retina, and carried out the functional analysis. A solute carrier family protein SLC4A2 was particularly analyzed because we found the protein is involved in the vacuole formation which has been reported to have a certain relation with the protein quality control system and ER stress. We found an amino acid substitution p. G26E of SLC4A2 in a glaucoma patient family and various differences between an oridinary type p. 26G and a variant p. 26E regarding the behavior. The differences included changes in the intracellular localization, fragmentation of SLC4A2 itself in p. 26E but not in p. 26G, and less extent of vacuolization in p. 26E than in p. 26G. From this, it was suggested that SLC4A2 plays some roles in the protein quality control. Furthermore, it was even possible to speculate that the insufficient formation of vacuoles caused by the amino acid change G26E is responsible for the onset of glaucoma. Our new finding on the function of OPTN in the protein quality control system may relate to the OPTN-containing inclusion body observed in the tissues of amyotrophic lateral sclerosis(ALS) patients.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (10 results)

All 2011 2010 2009

All Presentation (10 results)

  • [Presentation] 蛋白品質管理機構の破綻とERストレス発生の観点に基づく緑内障発症機構の分子解析:オプチニュリン相互作用蛋白SLC4A2の挙動と役割の検討(Molecular analysis of glaucoma-developing mechanism from a novel viewpoint based on the failure of endoplasmic reticulum quality control system : Investigation of an OPTN-interacting protein SLC4A2)2011

    • Author(s)
      大坪正史、高潔、堀田喜裕、蓑島伸生
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2011-12-14
    • Related Report
      2011 Final Research Report
  • [Presentation] 蛋白品質管理機構の破綻とERストレス発生の観点に基づく緑内障発症機構の分子解析:オプチニュリン相互作用蛋白SLC4A2の挙動と役割の検討2011

    • Author(s)
      大坪正史
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2011-12-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] タンパク品質管理系のOPTNによる制御とSLC4A2変異の検討2011

    • Author(s)
      大坪正史
    • Organizer
      第3回浜松医科学シンポジウム
    • Place of Presentation
      浜松医科大学(静岡県)
    • Year and Date
      2011-02-25
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] 緑内障原因遺伝子オプチニュリンによるタンパク品質管理系の制御の可能性の検討(The possibility for protein maintenance by glaucoma-causative gene OPTN)2010

    • Author(s)
      大坪正史、細野克博、高潔、Mary K. Wirtz、堀田喜裕、蓑島伸生
    • Organizer
      第33回日本分子生物学会・第83回日本生化学会合同大会(BMB2010)
    • Place of Presentation
      神戸ポートアイランド(兵庫県)
    • Year and Date
      2010-12-10
    • Related Report
      2011 Final Research Report
  • [Presentation] 緑内障原因遺伝子オプチニュリンによるタンパク品質管理系の制御の可能性の検討2010

    • Author(s)
      大坪正史
    • Organizer
      第33回日本分子生物学会・第83回日本生化学会 合同大会(BMB2010)
    • Place of Presentation
      神戸ポートアイランド(兵庫県)
    • Year and Date
      2010-12-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] Isolation of proteins interacting with optineurin, a glaucoma-causative gene product(緑内障原因遺伝子産物オプチニュリンと相互作用するタンパクの同定)2009

    • Author(s)
      大坪正史、Thanseem Ismail、細野克博、堀田喜裕、蓑島伸生
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2009-12-12
    • Related Report
      2011 Final Research Report
  • [Presentation] Isolation of proteins interacting with optineurin, a glaucoma-causative gene product (緑内障原因遺伝子産物オプチニュリンと相互作用するタンパクの同定)2009

    • Author(s)
      大坪正史, 他
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜 (神奈川県)
    • Year and Date
      2009-12-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] Isolation of proteins interacting with optineurin, a product protein of glaucoma-causative gene2009

    • Author(s)
      大坪正史(Masafumi Ohtsubo), Thanseem Ismail,細野克博(Katsuhiro Hosono), Ryo Asaoka, Chunxia Wang, Hiroshi Nakanishi, Hiroyuki Mineta, Yoshihiro Hotta, Shinsei Minoshima
    • Organizer
      第9回慶北-浜松合同医学シンポジウム
    • Place of Presentation
      慶北医科大学(中国)
    • Year and Date
      2009-09-25
    • Related Report
      2011 Final Research Report
  • [Presentation] Isolation of proteins interacting with optineurin, a product protein of glaucoma-causative gene2009

    • Author(s)
      大坪正史, 他
    • Organizer
      第9回慶北-浜松合同医学シンポジウム (The 9th Kyungpook-Hamamatsu Joint Medical Symposium, Hamamatsu Meeting)
    • Place of Presentation
      慶北大学 医科大学 (韓国)
    • Year and Date
      2009-09-25
    • Related Report
      2009 Annual Research Report
  • [Presentation] 緑内障原因遺伝子ミオシリンの相互作用蛋白の同定 : 発症を修飾する因子としての可能性2009

    • Author(s)
      大坪正史, 他
    • Organizer
      第113回日本眼科学会総会
    • Place of Presentation
      東京国際フォーラム (東京都)
    • Year and Date
      2009-04-16
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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