2021 Fiscal Year Final Research Report
Analysis of function of Hikeshi affecting cellular homeostasis
| Project/Area Number |
18H02442
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 44010:Cell biology-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Imamoto Naoko 国立研究開発法人理化学研究所, 開拓研究本部, 主任研究員 (20202145)
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| Co-Investigator(Kenkyū-buntansha) |
小瀬 真吾 国立研究開発法人理化学研究所, 開拓研究本部, 専任研究員 (90333278)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 核ー細胞質間輸送 / 分子シャペロンHsp70 / HSF1 / タンパク質毒性ストレス / Hikeshi / タンパク質の恒常性 |
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| Outline of Final Research Achievements |
The prime feature of eukaryotic cells is the separation of the intracellular space into two compartments, the nucleus and the cytoplasm. Active nuclear transport is crucial for the maintenance of this separation. In this study, we focus on a nuclear transport receptor named Hikeshi, which mediates the heat stress-induced nuclear import of Hsp70s. The cytoplasmic function of Hsp70 is well studied, but its nuclear roles remain obscure. We found Hikeshi regulates the nucleocytoplasmic distribution of Hsp70 not only under heat shock conditions but also under nonstressed conditions. Nuclear Hsp70 affects the transcriptional activity of HSF1 and nuclear proteostasis under nonstressed conditions. Depletion of Hikeshi induces a reduction in nuclear Hsp70 and activate HSF1 under nonstressed conditions, and impair the heat shock response. Thus, proper nucleocytoplasmic distribution of Hsp70, mediated by Hikeshi, is required for nuclear proteostasis and adaptive response to heat shock.
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| Free Research Field |
細胞生物学
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| Academic Significance and Societal Importance of the Research Achievements |
核-細胞質間輸送という、生体にとって基本的な細胞内反応の生理的重要性の一例を分子のレベルで具体的に明らかにすることができた意義は大きい。Hsp70はタンパク質の折りたたみや凝集阻止を担う分子シャペロンとして細胞質における機能が有名である。このHsp70を核に輸送する運搬体Hikeshiを同定したが、Hsp70の核内機能が不明であった。Hikeshiの解析から、核内Hsp70が、転写因子HSF1の活性を制御することで核内タンパク質の恒常性維持を担うことが明らかになった。その破綻は生体に重篤な作用を示す。核と細胞質という、真核生物の基本となる分子の細胞内局在の重要性が改めて示された。
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