Study on the mechanism of Girdin-mediated amino acid signaling and regulation of mTORC1 activity in cancer cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K21061
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology; Tumor biology
• Research Institution: Nagoya University
• Principal Investigator: Weng Liang 名古屋大学, 医学系研究科, 特任助教 (20729280)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: アミノ酸シグナル / mTORC1 / Girdin

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.

Free Research Field

実験病理学