| 研究実績の概要 |
In FY2016, we continued to analyze the interaction between Girdin and CD98/LAT1, and the effect of that interaction on mTORC1 activation.
1. In the previous year, we showed the direct interaction of Girdin and CD98hc (heavy chain). In FY2016, we further revealed that Girdin N-terminal domain (NT) is responsible for the interaction with the cytoplasmic region of CD98hc.
2. We found that MAPK directly phosphorylates Girdin, which is critical for the interaction with CD98hc. We found that this phosphorylation negatively regulates mTORC1 activation in 293 cells.
3. We further demonstrated that the ubiquitination of CD98hc cytoplasmic region is essential for its interaction with Girdin NT domain.
4. Finally, we showed that neural stem cells or neuroblasts found in the dentate gyrus and the rostral migratory stream in Girdin knock out mice showed high mTORC1 activation compared with control wild-type mice, supporting our findings on cultured cells that Girdin negatively regulates mTORC1 activity.
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