| Project/Area Number |
15K21061
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Experimental pathology
Tumor biology
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| Research Institution | Nagoya University |
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Principal Investigator |
Weng Liang 名古屋大学, 医学系研究科, 特任助教 (20729280)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | アミノ酸シグナル / mTORC1 / Girdin / Cell metabolism / mTOR |
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| Outline of Final Research Achievements |
Desensitization, which involves the downregulation of cell surface receptors, is a common negative regulatory process for cell signalings. Amino acid signaling mediated by the activation of mechanistic target of rapamycin complex 1 (mTORC1) is fundamental to cell growth and metabolism. However, how cells desensitize to amino acid signaling is unknown. Here, we show that interaction between 4F2 heavy chain (4F2hc), a subunit of multiple amino acid transporters, and the multifunctional hub protein Girdin downregulates mTORC1 activity. 4F2hc interacts with Girdin in mitogen-activated protein kinase- and amino acid signaling-dependent manners to translocate to the lysosome. The resultant decrease in cell-surface 4F2hc leads to lowered cytoplasmic glutamine content, which desensitizes cells to amino acid signaling. These findings uncovered the mechanism underlying desensitization of amino acid signaling, which may play a role in tightly regulated cell growth and metabolism.
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