Molecular Mechanism of Endoplasmic and Golgi Cation Pumps and Diseases Caused by Their Defects

• Project/Area Number: 18370058
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biophysics
• Research Institution: Asahikawa Medical College
• Principal Investigator: SUZUKI Hiroshi Asahikawa Medical College, 医学部, 教授 (50183421)
• Co-Investigator(Kenkyū-buntansha): DAIHO Takashi 旭川医科大学, 医学部, 准教授 (90207267) ; YAMASAKI Kazuo 旭川医科大学, 医学部, 助教 (60241428)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥17,540,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥2,340,000); Fiscal Year 2008: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2007: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2006: ¥7,400,000 (Direct Cost: ¥7,400,000)
• Keywords: Ca<2+>ポンプ / 小胞体 / Ca^<2+> / Mn^<2+>ポンプ / ゴルジ体 / ダリエー病 / ヘイリー・ヘイリー病 / 能動輸送 / Ca2+ポンプ / リン酸化中間体 / 構造アナログ / ATP分解 / エネルギー共役 / 機能ドメイン / Ca^<2+>ポンプ / ゴルジ装置 / 角化

Research Abstract

小胞体Ca^(2+)ポンプによるCa^(2+)輸送の仕組みについての理解を大きく進展させた。皮膚異常角化症(ダリエー病)の原因となる世界51家系の小胞体Ca^(2+)ポンプ遺伝子異常の夫々がCa^(2+)ポンプ蛋白にどのような異常を引き起こすかを明らかにした。また皮膚異常角化症(ヘイリー・ヘイリー病)の原因変異となるゴルジ体Ca^(2+)/Mn^(2+)ポンプは皮膚基底層に局在すること、この発現抑制が皮膚表皮細胞の分化(角化)の開始因子であることを発見した。

Research Products

• [Journal Article] Roles of Tyr^<122>-hydrophobic Cluster and K^+ Binding in Ca^<2+>-releasing Process of ADP-insensitive Phosphoenzyme of Sarcoplasmic Reticulum Ca^<2+>-ATPase (2008)
  • Author(s): Kazuo Yamasaki, Guoli Wang, Takashi Daiho, Stefania Danko, and Hiroshi Suzuki
  • Journal Title: The Journal of Biological Chemistry 283(43) Pages: 29144-29155
  • Peer Reviewed
• [Journal Article] Roles of Tyr^<122>-hydrophobic Cluster and K^+ Binding in Ca^<2+>-releasing Process of ADP-insensitive Phosphoenzyme of Sarcopl asmic Reticulum Ca^<2+>-ATPase (2008)
  • Author(s): Kazuo Yamasaki
  • Journal Title: Journal of Biological Chemistry 283-43 Pages: 29144-29155
  • Peer Reviewed
• [Journal Article] Critical Role of Glu^<40>-Ser^<48> Loop Linking Actuator Domain and First Transmembrane Helix of Ca^<2+>-ATPase in Ca^<2+> Deocclusion and Release from ADP-insensitive Phosphoenzyme (2007)
  • Author(s): Takashi Daiho, Kazuo Yamasaki, Stefania Danko, and Hiroshi Suzuki
  • Journal Title: The Journal of Biological Chemistry 282(47) Pages: 34429-34447
  • NAID: 120003182903
  • Peer Reviewed
• [Journal Article] Critical Role of Glu^<40>-Ser^<48> Loop Linking Actuator Domain and First Transmembrane Helix of Ca^<2+>-ATPase in Ca^<2+> Deocclusion and Release from ADP-insensitive Phosphoenzyme (2007)
  • Author(s): Takashi Daiho
  • Journal Title: Journal of Biological Chemistry 282・47 Pages: 34429-34447
  • NAID: 120003182903
  • Peer Reviewed
• [Journal Article] Comprehensive Analysis of Expression and Function of 51 Sarco(endo)plasmic Reticulum Ca^<2+>-ATPase Mutants Associated with Darier Disease (2006)
  • Author(s): Yuki Miyauchi, Takashi Daiho, Kazuo Yamasaki, Hidetoshi Takahashi, Akemi Ishida-Yamamoto, Stefania Danko, Hiroshi Suzuki, and Hajime Iizuka
  • Journal Title: The Journal of Biological Chemistry 281(32) Pages: 22882-22895
  • Peer Reviewed
• [Journal Article] ATP2C1 is specifically localized in the basal layer of normal epidermis and its depletion triggers keratinocyte differentiation (2006)
  • Author(s): Masaki Yoshida, Kazuo Yamasaki, Takashi Daiho, Hajime Iizuka, and Hiroshi Suzuki
  • Journal Title: Journal of Dermatological Science 43(1) Pages: 21-33
  • NAID: 10020549262
  • Peer Reviewed
• [Journal Article] Molecular Mechanism of Ca-ATPase and Diseases Caused by Its120-126 Defects (2006)
  • Author(s): Hiroshi Suzuki
  • Journal Title: (膜)Membrane 31(3) Pages: 120-126
• [Journal Article] ATP2C1 is specifically localized in the basal layer of normal epidermis and its depletion triggers keratinocyte differentiation (2006)
  • Author(s): Masaki Yoshida
  • Journal Title: Journal of Dermatological Science 43・1 Pages: 21-33
• [Journal Article] Comprehensive Analysis of Expression and Function of 51 Sarco(endo)plasmic Reticulum Ca^<2+>-ATPase Mutants Associated with Darier Disease (2006)
  • Author(s): Yuki Miyauchi
  • Journal Title: The Journal of Biological Chemistry 281・32 Pages: 22882-22895
• [Journal Article] Molecular Mechanism of Ca-ATPase and Diseases Caused by Its Defects (2006)
  • Author(s): Hiroshi Suzuki
  • Journal Title: (膜)Membrane 31・3 Pages: 120-126
  • NAID: 10017581392
• [Journal Article] Role of the regions linking cytoplasmic and transmembrane domains in processing of phosphorylated intermediates for Ca^<2+> transport of sarcoplasmic reticulum Ca^<2+>-ATPase (2006)
  • Author(s): Takashi Daiho
  • Journal Title: 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress ABSTRACTS Pages: 125-125
• [Journal Article] The Ca^<2+> bound ADP-insensitive Phosphoenzyme of Sarcoplasmic Reticulum Ca^<2+>-ATPase Mutant (2006)
  • Author(s): Kazuo Yamasaki
  • Journal Title: 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress ABSTRACTS Pages: 125-125
• [Presentation] Ca^<2+>ポンプの分子作動機構 : 部位特異的変異およびリン酸化中間体アナログの開発と構造解析による理解 (2009)
  • Author(s): 鈴木裕
  • Organizer: 日本薬学会第129年会(招待講演)
  • Place of Presentation: 京都
  • Year and Date: 2009-03-27
• [Presentation] Ca^<2+>ポンプの分子作動機構 : 部位特異的変異およびリン酸化中間体アナログの開発と構造解析による理解 (2009)
  • Author(s): 鈴木裕
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
  • Year and Date: 2009-03-27
• [Presentation] 筋小胞体Ca^<2+>-ATPaseのCa^<2+>結合型-リン酸化中間体アナログの安定性に及ぼすヌクレオチドの効果 (2008)
  • Author(s): 大保貴嗣
  • 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: 日神戸
  • Year and Date: 2008-12-10
• [Presentation] 筋小胞体Ca^<2+>-ATPaseのE2PCa_2におけるTyr^<122>-Hydrophobic clusterの果たす役割について (2008)
  • Author(s): 山崎和生
  • 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: 日神戸
  • Year and Date: 2008-12-10
• [Presentation] 筋小胞体Ca^<2+>-ATPaseのCa^<2+>結合型-リン酸化中間体アナログの安定性に及ぼすヌクレオチドの効果 (2008)
  • Author(s): 大保貴嗣
  • 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: 2008-12-10
• [Presentation] 筋小胞体Ca^<2+>-ATPaseのE2PCa_2におけるTyr^<122>-Hydrophobic clusterの果たす役割について (2008)
  • Author(s): 山崎和生
  • 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: 2008-12-10
• [Presentation] Roles of interactions between Actuator-and Nucleotide Binding-domains of Ca^<2+>-ATPase (2008)
  • Author(s): Liu Xiaoyu
  • 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: 2008-12-10
• [Presentation] Ca^<2+>ポンプの輸送機構-部位特異的変異およびリン酸化中間体アナログの開発と構造解析による理解 (2008)
  • Author(s): 鈴木裕
  • Organizer: 日本生体エネルギー研究会第34回討論会(招請講演)
  • Place of Presentation: 東京
  • Year and Date: 2008-11-17
• [Presentation] Ca^<2+>ポンプの輸送機構-部位特異的変異およびリン酸化中間体アナログの開発と構造解析による理解 (2008)
  • Author(s): 鈴木裕
  • Organizer: 日本生体エネルギー研究会第34回討論会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-07
• [Presentation] 筋小胞体Ca^<2+>-ATPaseのリン酸化中間体の転換およびCa2+輸送におよぼすヌクレオチドの顕著な効果 (2008)
  • Author(s): 大保貴嗣
  • Organizer: 日本生体エネルギー研究会第34回討論会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-07
• [Presentation] 筋小胞体Ca^<2+>-ATPaseのP-Nドメインヒンジ領域に存在する荷電側鎖の役割と一価イオンの影響 (2008)
  • Author(s): 山崎和生
  • Organizer: 日本生体エネルギー研究会第34回討論会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-07
• [Presentation] Roles of the A domain and its linkers of sarco(endo)plasmic reticulum Ca^<2+> pump for processing the phosphorylated intermediates and Ca^<2+> release (2008)
  • Author(s): Hiroshi Suzuki
  • Organizer: 12th International ATPase Conference(招請講演)
  • Place of Presentation: デンマーク・オーフス
  • Year and Date: 2008-08-06
• [Presentation] Critical Role of Glu^<40>-Ser^<48> Loop Linking Actuator Domain and First Transmembrane Helix of Ca^<2+>-ATPase in Ca^<2+> Deocclusion and Release from ADP-insensitive Phosphoenzyme (2008)
  • Author(s): Takashi Daiho
  • Organizer: 12th International ATPase Conference
  • Place of Presentation: デンマーク・オーフス
  • Year and Date: 2008-08-06
• [Presentation] Roles of Tyr^<122>-Hydrophobic cluster and K+ binding in Ca^<2+>-releasing Process of ADP-insensitive Phosphoenzyme of Sarcoplasmic Reticulum Ca^<2+>-ATPase (2008)
  • Author(s): Kazuo Yamasaki
  • Organizer: 12th International ATPase Conference
  • Place of Presentation: デンマーク・オーフス
  • Year and Date: 2008-08-06
• [Presentation] Roles of the A domain and its linkers of sarco(endo)plasmic reticulum Ca^<2+> pump for processing the phosphorylated intermediates and Ca^<2+> release (2008)
  • Author(s): Hiroshi Suzuki
  • Organizer: 12th International ATPase Conference
  • Place of Presentation: デンマーク・オーフス
  • Year and Date: 2008-08-06
• [Presentation] Roles of Tyr^<122>-Hydrophobic cluster and K^+ binding in Ca^<2+>-releasing Process of ADP-insensitive Phosphoenzyme of Sarcoplasmic Reticulum Ca^<2+>-ATPase (2008)
  • Author(s): Kazuo Yamasaki
  • Organizer: 12th International ATPase Conference
  • Place of Presentation: デンマーク・オーフス
  • Year and Date: 2008-08-06
• [Presentation] 筋小胞体Ca^<2+>-ATPaseの変異体によるCa^<2+>を閉塞したADP非感受性リン酸化中間体のアナログの形成 (2007)
  • Author(s): 大保貴嗣
  • 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: 2007-12-14
• [Presentation] 筋小胞体Ca^<2+>-ATPaseのCa^<2+>放出過程におけるTyr^<122>-Hydrophobic clusterとK^+との関連 (2007)
  • Author(s): 山崎和生
  • 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: 2007-12-14
• [Presentation] 筋小胞体Ca^<2+>-ATPaseの変異体によるCa^<2+>を閉塞したADP非感受性リン酸化中間体のアナログの形成 (2007)
  • Author(s): 大保 貴嗣
  • 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: 2007-12-14
• [Presentation] 筋小胞体Ca^<2+>-ATPaseのCa^<2+>放出過程におけるTyr122-Hydrophobic clusterとK+との関連 (2007)
  • Author(s): 山崎 和生
  • 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: 2007-12-14
• [Presentation] 筋小胞体カルシウムポンプ:リン酸体中間体の転換にともなうCa^<2+>の脱閉塞機構 (2007)
  • Author(s): 大保 貴嗣
  • Organizer: 日本生体エネルギー研究会
  • Place of Presentation: 山口
  • Year and Date: 2007-11-16
• [Presentation] 筋小胞体Ca^<2+>-ATPaseのP-Nヒンジ領域に存在する荷電側鎖の役割 (2007)
  • Author(s): 山崎 和生
  • Organizer: 日本生体エネルギー研究会
  • Place of Presentation: 山口
  • Year and Date: 2007-11-16
• [Presentation] Molecular mechanism of Ca^<2+>-ATPase and Darier disease caused by its defects (2006)
  • Author(s): Hiroshi Suzuki
  • Organizer: 国際会議 "Molecular Mechanism and Regulation in Cation Transport ATPases and Related Genetic Diseases" 特別講演
  • Place of Presentation: 京都
  • Year and Date: 2006-06-16
• [Presentation] Critical Role of the A-domain/M1 Linker of Ca^<2+-> ATPase in Ca^<2+> Release into Lumen from ADP-insensitive Phosphoenzyme with Occluded Ca^<2+> (2006)
  • Author(s): Takashi Daiho
  • Organizer: Molecular Mechanism and Regulation in Cation Transport ATPases and Related Genetic Diseases(20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress)
  • Place of Presentation: 京都
• [Presentation] Critical Role of Tyr^<122> in Ca^<2+>-release from ADP-insensitive Phosphoenzyme of Sarcoplasmic Reticulum Ca^<2+>-ATPase (2006)
  • Author(s): Kazuo Yamasaki
  • Organizer: Molecular Mechanism and Regulation in Cation Transport ATPases and Related Genetic Diseases(20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress)
  • Place of Presentation: 京都
• [Remarks]
  • URL: http://www.asahikawa-med.ac.jp/dept/mc/biochem2/
• [Remarks] 主催国際会議 : Molecular Mechanism and Regulation in Cation Transport ATPases and Related Genetic Diseases(カチオン輸送ATPase : 分子機構と制御、そしてゲノム異常と病態) : 平成18年6月16-18日、京都にて主催した。当該研究分野の著名な研究者の殆ど全てと多くの若手研究者が集い高いレベルの発表と議論が展開され、今後の本分野発展の礎となった。
  • URL: http://www.asahikawa-med.ac.jp/dept/mc/biochem2/cationpumps2006kyoto/home.html
• [Remarks]
  • URL: http://www.asahikawa-med.ac.jp/dept/mc/biochem2/