Substrate-induced degradation of yeast amino acid permeases and the autodegradation-signaling associated with dynamic structural changes
| Project/Area Number |
18K05397
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 38020:Applied microbiology-related
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| Research Institution | Aoyama Gakuin University |
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Principal Investigator |
Abe Fumiyoshi 青山学院大学, 理工学部, 教授 (30360746)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 酵母アミノ酸輸送体 / 動的構造変化 / 自己分解シグナル / 出芽酵母 / トリプトファン輸送体 / ユビキチン分解 / 基質輸送 / アイソソーム / アミノ酸輸送体 / トリプトファン輸送体Tat2 / Eisosome / ユビキチン依存性分解 / 高圧増殖 / Ehg1/May24 / 栄養源センシング / ユビキチン化 |
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| Outline of Final Research Achievements |
Nutrient starvation is a life-threatening stress while nutrient excess is also toxic in microorganisms. Among two yeast tryptophan permeases, Tat1 (the low-affinity type) was stably expressed in the plasma membrane whereas Tat2 (the high-affinity type) was rapidly degraded upon substrate addition. The D74R mutation in the acidic patch in the cytoplasmic domain abolished the substrate-induced Tat2 degradation. We hypothesize that the dynamic structural changes associated the substrate imports transmit the autodegradation signal of Tat2 allowing its own ubiquitination. We also explored cellular responses to nutrient limitation from aspects of poorly-characterized proteins and TORC1.
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| Academic Significance and Societal Importance of the Research Achievements |
トリプトファンの動態は、細胞内NAD+の調節、トリプトフォールやセロトニンなど細胞間伝達物質の合成、ヒトではトリプトファン輸送体MCT10が甲状腺ホルモンの輸送を担うなど、他のアミノ酸にはないユニークさがある。またトリプトファンは希少なアミノ酸であるうえ、ヒトの必須アミノ酸でもある。よって低濃度トリプトファン条件下における取り込みと、それとは逆に基質過剰時の取り込み抑制が特に重要だ。本研究で得られた成果は、酵母のトリプトファン輸送体Tat2が広範な生物種におけるトリプトファン制御のモデルとなることを示すとともに、１タンパク質分子がシグナルの受容と伝達を同時に担うユニークな側面を映し出している。
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Over-expression of Caj1, a plasma membrane associated J-domain protein in Saccharomyces cerevisiae stabilizes amino acid permeases.2020
Author(s)
Dobriyala, N., Sagarikaa, P., Shrivastavaa, A., Vermaa, A.K., Islama, Z., Guptaa, P. , Mochizuki, T., Abe, F., Sahi, C.
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Journal Title
Biochim. Biophys. Acta
Volume: 1862
Issue: 11
Pages: 183435-183435
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] A novel ER membrane protein Ehg1/May24 plays a critical role in maintaining multiple nutrient permeases in yeast under high-pressure perturbation.2019
Author(s)
1. Kurosaka, G., Uemura, S., Mochizuki, T., Kozaki, Y., Hozumi, A., Suwa, S., Ishii, R., Kato, Y., Imura, S., Ishida, N., Noda, Y., and Abe, F
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Journal Title
Sci. Rep.
Volume: 9
Issue: 1
Pages: 18341-18341
DOI
Related Report
Peer Reviewed / Open Access
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