2018 Fiscal Year Final Research Report
Membrane topogenesis and quality control of tail-anchored proteins (TAs)
| Project Area | Nascent-chain Biology |
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| Project/Area Number |
26116007
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kyushu University |
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Principal Investigator |
Fujiki Yukio 九州大学, 生体防御医学研究所, 特任教授 (70261237)
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| Co-Investigator(Kenkyū-buntansha) |
田村 茂彦 九州大学, 基幹教育院, 教授 (90236753)
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| Research Collaborator |
OKUMOTO kanji 九州大学, 理学研究院
HONSHO masanori 九州大学, 生体防御医学研究所
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| Project Period (FY) |
2014-07-10 – 2019-03-31
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| Keywords | 新生鎖 / テイルアンカー型タンパク質 / オルガネラ選別輸送 / 膜挿入機構 / 品質管理機構 / オルガネラ恒常性 / 酸化ストレス応答 |
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| Outline of Final Research Achievements |
Peroxisome homeostasis involving regulation of the number and metabolic functions is maintained by coordinating biogenesis, division, and degradation. Tail-anchored (TA) proteins localized by a single C-terminal transmembrane domain are found in all cellular membranes. Peroxisomal TAs were investigated in this research. A number of outcomes include 1) TA proteins to peroxisomes are targeted via the Pex19p- and Pex3p-dependent Class-I pathway. 2) VDAC2 was identified as restoring ZP114, a CHO cell mutant lacking peroxisome. We also discovered that the catalase released from peroxisomes via BAK pore eliminates H2O2, a toxic and major causative of the oxidative stress, in the cytosol for cell survival. 3) We discovered that the 17-kDa nucleoside diphosphate kinase-like protein, DYNAMO1, locally generates GTP in mitochondrial division and peroxisome-dividing machineries. These outstanding contributions to organelle homeostasis in molecular cell biology are highly appreciated.
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| Free Research Field |
分子細胞生物学、細胞機能とオルガネラホメオスタシス
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| Academic Significance and Societal Importance of the Research Achievements |
細胞機能の発現は、新生タンパク質の細胞内小器官への選別輸送・局在化により実現される。TA膜タンパク質は細胞総膜タンパク質の3~5%を占め300~400種が存在、物質輸送や細胞内情報伝達などの生命活動を担う。本研究では、ペルオキシソームTAの膜標的化とペルオキシソーム機能制御の分子機構解明に取り組んだ。代表的成果として、細胞死因子BAKによる細胞死防御戦略の発見、ペルオキシソームやミトコンドリアの分裂に必須なGTP供給因子Dynamo1の発見がある。多くの新知見は他のオルガネラ局在性TA輸送だけでなく、オルガネラ膜タンパク質や可溶性タンパク質の輸送・品質管理機構の解明に大きな波及効果を有する。
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