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Identification and the physiological role of a cystine transporter

Research Project

Project/Area Number 24591198
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Kidney internal medicine
Research InstitutionOsaka University

Principal Investigator

NAGAMORI Shushi  大阪大学, 医学(系)研究科(研究院), 准教授 (90467572)

Co-Investigator(Kenkyū-buntansha) OHGAKI Ryuichi  大阪大学, 大学院医学系研究科, 助教 (20467525)
NISHIZONO Hirofumi  富山大学, 生命科学先端研究センター, 助教 (10502289)
Co-Investigator(Renkei-kenkyūsha) KANAI Yoshikatsu  大阪大学, 大学院医学系研究科, 教授 (60204533)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsシスチン尿症 / アミノ酸トランスポーター / 腎臓 / ヘテロダイマー / トランスポーター / アミノ酸 / ヘテロ二量体 / 再構成系 / 機能共役 / 膜複合体 / プロテオミクス
Outline of Final Research Achievements

The heterodimeric amino acids transporter (HAT) family, which consists of heavy chains (Slc3) and light chains (Slc7), has important roles for amino acid transports in many types of organs. Among the family, rBAT forms a heterodimeric complex only with b0,+AT. Mutations in the two genes cause cystinuria, an autosomal recessive disorder of renal reabsorption of cystine at the apical membranes of proximal tubules. However, the expression paradox of the proteins has been remaining. While rBAT highly express in the S3 segment of the proximal tubules, the expression of b0,+AT decrease from the S1 to the S3 segment. In this study, Slc7a13, one of the HAT family members with an unknown heavy chain, was found to form a heterodimer with rBAT. Slc7a13 was expressed dominantly in the S3 segment and transported cystine. These findings strongly indicate that Slc7a13 is the secondary cystine transporter at the S3 segment in the kidney, which was postulated the presence in 70’s.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (41 results)

All 2015 2014 2013 2012 Other

All Journal Article (17 results) (of which Peer Reviewed: 16 results,  Open Access: 4 results,  Acknowledgement Compliant: 3 results) Presentation (24 results) (of which Invited: 12 results)

  • [Journal Article] Development of a Widely Usable Amino Acid Tracer: 76Br-α-Methyl-Phenylalanine for Tumor PET Imaging.2015

    • Author(s)
      Hanaoka H, Ohshima Y, Suzuki Y, Yamaguchi A, Watanabe S, Uehara T, Nagamori S, Kanai Y, Ishioka NS, Tsushima Y, Endo K, Arano Y.
    • Journal Title

      J Nucl Med.

      Volume: in press

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Boronophenylalanine, a boron delivery agent for boron neutron capture therapy, is transported by ATB(0,+) , LAT1 and LAT2.2015

    • Author(s)
      Wongthai P, Hagiwara K, Miyoshi Y, Wiriyasermkul P, Wei L, Ohgaki R, Kato I, Hamase K, Nagamori S, Kanai Y.
    • Journal Title

      Cancer Sci.

      Volume: 106 Issue: 3 Pages: 279-86

    • DOI

      10.1111/cas.12602

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] NPT1/SLC17A1 is a renal urate exporter in humans and its common gain-of-function variant decreases the risk of renal underexcretion gout.2015

    • Author(s)
      Chiba T, Matsuo H, Kawamura Y, Nagamori S, Nishiyama T, Wei L, Nakayama A, Nakamura T, Sakiyama M, Takada T, Taketani Y, Suma S, Naito M, Oda T, Kumagai H, Moriyama Y, Ichida K, Shimizu T, Kanai Y, Shinomiya N.
    • Journal Title

      Arthritis Rheumatol.

      Volume: 67(1) Issue: 1 Pages: 281-287

    • DOI

      10.1002/art.38884

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] プロテオミクスを用いたトランスポーターの網羅的発現変動解析2015

    • Author(s)
      永森收志、金井好克
    • Journal Title

      遺伝: 生物の科学

      Volume: 69 Pages: 47-51

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Expression of amino acid transporters (LAT1, ASCT2 and xCT) as clinical significance in hepatocellular carcinoma.2014

    • Author(s)
      Namikawa M, Kakizaki S, Kaira K, Tojima H, Yamazaki Y, Horiguchi N, Sato K, Oriuchi N, Tominaga H, Sunose Y, Nagamori S, Kanai Y, Oyama T, Takeyoshi I, Yamada M.
    • Journal Title

      Hepatol Res.

      Volume: in press Issue: 9 Pages: 1014-1022

    • DOI

      10.1111/hepr.12431

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xCT) in surgically resected tongue cancer.2014

    • Author(s)
      Toyoda M, Kaira K, Ohshima Y, Ishioka NS, Shino M, Sakakura K, Takayasu Y, Takahashi K, Tominaga H, Oriuchi N, Nagamori S, Kanai Y, Oyama T, Chikamatsu K.
    • Journal Title

      Br J Cancer

      Volume: 110 Pages: 2506-13

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter, sodium taurocholate cotransporting polypeptide (NTCP)2014

    • Author(s)
      Watashi K, Sluder A, Daito T, Matsunaga S, Ryo A, Nagamori S, Iwamoto M, Nakajima S, Tsukuda S, Borroto-Esoda K, Sugiyama M, Tanaka Y, Kanai Y, Kusuhara H, Mizokami M, Wakita T
    • Journal Title

      Hepatology

      Volume: 59 Issue: 5 Pages: 1726-1737

    • DOI

      10.1002/hep.26982

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Annexin A4-conferred platinum resistance is mediated by the copper transporter ATP7A2014

    • Author(s)
      Matsuzaki S, Enomoto T, Serada S, Yoshino K, Nagamori S, Morimoto A, Yokoyama T, Kim A, Kimura T, Ueda Y, Fujita M, Fujimoto M, Kanai Y, Kimura T, Naka T
    • Journal Title

      Int J Cancer

      Volume: 134 Issue: 8 Pages: 1796-1809

    • DOI

      10.1002/ijc.28526

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nicotine induces dendritic spine remodeling in cultured hippocampal neurons.2014

    • Author(s)
      Oda A^1, Yamagata K, Nakagomi S, Uejima H, Wiriyasermkul P, Ohgaki R, Nagamori S, Kanai Y, Tanaka H.
    • Journal Title

      J Neurochem.

      Volume: 128(2) Issue: 2 Pages: 246-255

    • DOI

      10.1111/jnc.12470

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical significance of L-type amino acid transporter 1 expression as a prognostic marker and potential of new targeting therapy in biliary tract cancer2013

    • Author(s)
      Kaira K, Sunose Y, Ohshima Y, Ishioka NS, Arakawa K, Ogawa T, Sunaga N, Shimizu K, Tominaga H, Oriuchi N, Itoh H, Nagamori S, Kanai Y, Yamaguchi A, Segawa A, Ide M, Mori M, Oyama T, Takeyoshi I
    • Journal Title

      BMC Cancer

      Volume: 16 Issue: 1 Pages: 482-482

    • DOI

      10.1186/1471-2407-13-482

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] YY1 binds to α-synuclein 3'-flanking region SNP and stimulates antisense noncoding RNA expression.2013

    • Author(s)
      Mizuta I, Takafuji K, Ando Y, Satake W, Kanagawa M, Kobayashi K, Nagamori S, Shinohara T, Ito C, Yamamoto M, Hattori N, Murata M, Kanai Y, Murayama S, Nakagawa M, Toda T.
    • Journal Title

      J Hum Genet

      Volume: 58 Issue: 11 Pages: 711-719

    • DOI

      10.1038/jhg.2013.90

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Biological evaluation of 3-[18F]fluoro-α-methyl-D-tyrosine (D-[18F]FAMT) as a novel amino acid tracer for positron emission tomography.2013

    • Author(s)
      Ohshima Y
    • Journal Title

      Ann Nucl Med

      Volume: 27 Issue: 4 Pages: 314-324

    • DOI

      10.1007/s12149-013-0687-7

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Glycolipozyme MPIase is essential for topology inversion of SecG during preprotein translocation2012

    • Author(s)
      Moser, M., Nagamori, S., Huber, M., Tokuda, H., Nishiyama, K.
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: (in press) Issue: 24 Pages: 9734-9739

    • DOI

      10.1073/pnas.1303160110

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] NRFL-1, the C. elegans NHERF Orthologue, Interacts with Amino Acid Transporter 6 (AAT-6) for Age-Dependent Maintenance of AAT-6 on the Membrane.2012

    • Author(s)
      Kohei Hagiwara
    • Journal Title

      Plos one

      Volume: 7(8) Issue: 8 Pages: e43050-e43050

    • DOI

      10.1371/journal.pone.0043050

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Establishment of Stable Cell Lines With High Expression of Heterodimers of Human 4F2hc and Human Amino Acid Transporter LAT1 or LAT2 and Delineation of Their Differential Interaction With <I>&alpha;</I>-Alkyl Moieties2012

    • Author(s)
      Narakorn Khunweeraphong
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 119 Issue: 4 Pages: 368-380

    • DOI

      10.1254/jphs.12124FP

    • NAID

      10031071638

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transport of 3-fluoro-L-α-methyl-tyrosine by tumor-upregulated L-type amino acid transporter 1: a cause of the tumor uptake in PET.2012

    • Author(s)
      Wiriyasermkul P, Nagamori S, Tominaga H, Oriuchi N, Kaira K, Nakao H, Kitashoji T, Ohgaki R, Tanaka H, Endou H, Endo K, Sakurai H, Kanai Y.
    • Journal Title

      J Nucl Med.

      Volume: 53 Issue: 8 Pages: 1253-1261

    • DOI

      10.2967/jnumed.112.103069

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Linkage of N-cadherin to multiple cytoskeletal elements revealed by a proteomic approach in hippocampal neurons.2012

    • Author(s)
      Tanaka H, Takafuji K, Taguchi A, Wiriyasermkul P, Ohgaki R, Nagamori S, Suh PG, Kanai Y.
    • Journal Title

      Neurochem Int.

      Volume: 61 Issue: 2 Pages: 240-250

    • DOI

      10.1016/j.neuint.2012.05.008

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Nagamori S and Kanai Y, Identification of a new heterodimeric amino acid transporter in the apical membrane of renal proximal tubule.2015

    • Author(s)
      Nagamori S and Kanai Y
    • Organizer
      第120回 日本解剖学会総会・全国学術集会・第92回 日本生理学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-22
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] A new cystine transporter in S3 segment of the renal proximal tubule is an “unknown-partner” of Slc3a1 (rBAT).2015

    • Author(s)
      Nagamori S.
    • Organizer
      The final HD physiology Symposium
    • Place of Presentation
      大阪
    • Year and Date
      2015-03-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] トランスポーターの網羅的プロテオミクスによるアミノ酸輸送系のプロファイリングと変動解析2014

    • Author(s)
      永森收志
    • Organizer
      第19回アミノ酸セミナー
    • Place of Presentation
      東京
    • Year and Date
      2014-12-05
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Transportsomes; the physical and/or functional complexes of transporters2014

    • Author(s)
      Nagamori S.
    • Organizer
      The 2nd International Symposium on Epithelial Barrier and Transport
    • Place of Presentation
      滋賀
    • Year and Date
      2014-11-01
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 腎近位尿細管におけるアミノ酸輸送複合体の解析2014

    • Author(s)
      永森收志
    • Organizer
      2014年度生理研研究会「粘膜免疫学と膜輸送生理学の融合」
    • Place of Presentation
      岡崎
    • Year and Date
      2014-10-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] アミノ酸トランスポーターを標的とした創薬研究から見えてきた 標的分子の新たな機2014

    • Author(s)
      永森收志
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 栄養とトランスポーター:アミノ酸の場合2014

    • Author(s)
      永森收志
    • Organizer
      第349回大阪大学臨床栄養研究会
    • Place of Presentation
      大阪
    • Year and Date
      2014-07-28
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] A new cystine transporter in S3 segment of the renal proximal tubule is an “unknown-partner” of Slc3a1 (rBAT)2014

    • Author(s)
      Nagamori S
    • Organizer
      Gordon Research Conference Membrane Transport Proteins
    • Place of Presentation
      West Dover, VT, United States
    • Year and Date
      2014-07-13 – 2014-07-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] A novel cystine transporter in S3 segment of the renal proximal tubule is an “unknown-partner” of Slc3a1 (rBAT)2013

    • Author(s)
      Shushi Nagamori, Pattama Wiriyasermkul, Meritxell Espino Guarch, Kazuhisa Okuyama, Saya Nakagomi, Kenijiro Tadagaki, Kazuaki Takafuji, Ryuichi Ohgaki, Manuel Palacín, Yoshikatsu Kanai
    • Organizer
      2nd HDP international symposium on Multi-Level Systems Biology
    • Place of Presentation
      Marunouchi, Tokyo
    • Related Report
      2013 Research-status Report
  • [Presentation] アミノ酸輸送体LAT1によって取り込まれたロイシンに対する細胞応答のリン酸プロテオミクスによる解析2013

    • Author(s)
      永森收志、Pattama Wiriyasermkul、世良田聡、仲哲治、金井好克
    • Organizer
      日本アミノ酸学会第7回学術大会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] アミノ酸トランスポーターと細胞内アミノ酸シグナリング2013

    • Author(s)
      永森 收志
    • Organizer
      生理学研究所研究会「細胞センサーの分子機構・相互関連・ネットワーク研究会」
    • Place of Presentation
      岡崎、愛知
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Functional coupling between a Na+-dependent anion transporter SMCT2 and a urate-anion exchanger URAT1 through a scaffold protein PDZK1.2012

    • Author(s)
      Shushi Nagamori, Yasuhiro Umemura, Pattama Wiriyasermkul, Saya Nakagomi, Yumiko Nishinaka, Kazuaki Takafuji, Ryuichi Ohgaki, Yoshikatsu Kanai.
    • Organizer
      Gordon Research Conferences, Membrane Transport Proteins.
    • Place of Presentation
      Les Diablerets, Switzerland
    • Related Report
      2012 Research-status Report
  • [Presentation] Functional coupling of transporters in a complex

    • Author(s)
      Shushi Nagamori
    • Organizer
      First Awaji International Workshop on “Electron Spin Science & Technology: Biological and Materials Science Oriented Applications”
    • Place of Presentation
      Awaji, Hyogo
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 「がん細胞のアミノ酸トランスポーター」

    • Author(s)
      永森收志、金井好克
    • Organizer
      第31回日本ヒト細胞学会学術集会 シンポジウム「分子標的診断・治療の進歩と今後」
    • Place of Presentation
      所沢、埼玉
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 日本人型シスチン尿症を発症させるアミノ酸トランスポーター変異体の機能解析

    • Author(s)
      永森 收志、河本 泰治、Pattama Wiriyasermkul、金井 好克
    • Organizer
      生理学研究所研究会「上皮膜輸送の多層的コントロールによる生体の恒常性維持機構」
    • Place of Presentation
      岡崎、愛知
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Metabolomics and proteomics analyses of knockout mice reveal real physiological substrates of an organic anion transporter.

    • Author(s)
      Shushi Nagamori, Xi He, Taku Hirata, Pattama Wiriyasermkul, Saya Nakagomi, Takamasa Ishikawa, Tomoyoshi Soga, Yoshikatsu Kanai
    • Organizer
      第86回日本生化学会大会、International Session
    • Place of Presentation
      横浜、神奈川
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 膜輸送複合体におけるトランスポーターの機能共役

    • Author(s)
      永森收志
    • Organizer
      第4回難治疾患共同研究拠点シンポジウム
    • Place of Presentation
      お茶の水、東京
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Functional coupling of a urate-anion exchanger URAT1 and Na+-dependent anion transporter SMCT2 on a PDZK1 scaffold; Proposal of “Transportsome” for urate-transport

    • Author(s)
      Shushi Nagamori, Yasuhiro Umemura, Pattama Wiriyasermkul, Yumiko Nishinaka, Noriyoshi Isozumi, Yoshikatsu Kanai
    • Organizer
      The 58th Annual Meeting of the Biophysical Society
    • Place of Presentation
      San Francisco、USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Evaluation of amino acid transporter LAT1 as a molecular target of anti-tumor therapy by means of the combination of comprehensive proteomics and transport assay網羅的プロテオミクスと輸送解析によるアミノ酸トランスポーター LAT1の抗腫瘍薬分子標的としての意義の検討

    • Author(s)
      永森 收志、Pattama Wiriyasermkul、五十棲 規嘉、Pornparn Kongpracha、大垣 隆一、金井 好克
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Related Report
      2013 Research-status Report
  • [Presentation] 網羅的定量オミクスによるトランスポーター研究の新しい展開 Comprehensive and quantitative "omics" bring up new world of transporter research

    • Author(s)
      永森收志、金井好克
    • Organizer
      2014年度日本農芸化学会 シンポジウム「トランスポーターを通して見る生命現象」
    • Place of Presentation
      生田、東京
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 日本人型シスチン尿症を発症させるアミノ酸トランスポーター変異体の機能解析

    • Author(s)
      河本泰治, 永森收志, Pattama Wiriyasermkul,金井好克
    • Organizer
      日本生化学会近畿部会
    • Place of Presentation
      宇治市
    • Related Report
      2012 Research-status Report
  • [Presentation] 腎尿細管に残された第二のシスチントランスポーターの分子同定

    • Author(s)
      大垣 隆一, 奥山 裕久, Pattama Wiriyasermkul, 中込 咲綾, 西中 由美子, 高藤 和輝, 永森 收志, 金井 好克
    • Organizer
      第3回分子腎臓フォーラム
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 腎近位尿細管の第二のシスチントランスポーターの分子同定と機能解析

    • Author(s)
      永森收志、奥山 裕久、Pattama Wiriyasermkul、中込 咲綾、西中 由美子、高藤 和輝、大垣 隆一、金井 好克
    • Organizer
      生理研研究会『粘膜防御における上皮膜輸送の役割とその破綻による疾病発症メカニズム』
    • Place of Presentation
      岡崎
    • Related Report
      2012 Research-status Report
  • [Presentation] 質量分析計と再構成プロテオリポソームを用いた新規トランスポーター複合体の解析-腎尿細管に残された第二のシスチントランスポーターの分子同定

    • Author(s)
      永森收志、奥山 裕久、Pattama Wiriyasermkul、中込 咲綾、西中 由美子、高藤 和輝、大垣 隆一、金井 好克
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡市
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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