2023 Fiscal Year Final Research Report
The study on the regulation and the physiological role of a vacuolar amino acid exporter Avt4
| Project/Area Number |
21K05507
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 38060:Applied molecular and cellular biology-related
|
|---|
| Research Institution | Ehime University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2021-04-01 – 2024-03-31
|
| Keywords | 液胞 / トランスポーター / TORC1 / オートファジー / アミノ酸 |
|---|
| Outline of Final Research Achievements |
By proximity biotinylation method, TORC1 and its related factors were suggested to interact with Avt4, a vacuolar amino acid exporter. Deletion of those genes suppressed the phosphorylation of Avt4. Alanine substitution of phosphorylation sites in Avt4 reduced the vacuolar amino acids, implying the elevation of vacuolar amino acid export. The growth recovery in the presence of TORC1 inhibitor and the phosphorylation of the TORC1 substrate in AVT4 knockout cells suggested that Avt4 downregulates the TORC1 activity. These propose that Avt4 and TORC1 are mutually regulated.
As to physiological role of Avt4, the elevation of catalase level under nitrogen starvation was suppressed and the incorporation 14C-labelled valine into proteins was noticeably reduced by multiple deletion of vacuolar amino acid exporters including Avt4. These suggest that the vacuolar amino acid export substantially contributes to the maintenance of protein synthesis under nitrogen starvation.
|
| Free Research Field |
細胞生物学
|
| Academic Significance and Societal Importance of the Research Achievements |
液胞／リソソームアミノ酸輸送は細胞内アミノ酸ホメオスタシスに重要な役割を果たす。その基幹装置であるアミノ酸トランスポーターの同定に続く次の課題として、その活性調節機構について新たな知見を得た。さらにトランスポーターがTORC1によって制御される一方で、直接的にTORC1の制御にも関わることが示唆された。このことは栄養情報伝達下流で機能するトランスポーターがレセプターとして上流因子に作用する新たな機構モデルを提案している。またトランスポーター多重欠損による表現型発現機構について分子レベルでの知見が得られ、活性調節機構解明と合わせ当該分野の研究を加速させる基盤を構築することができた。
|
