Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Mislocalization of TORC1 to Lysosomes Caused by KIF11 Inhibition Leads to Aberrant TORC1 Activity

  • Jang, Yoon-Gu (Institute of Molecular Biology and Genetics, Seoul National University) ;
  • Choi, Yujin (Institute of Molecular Biology and Genetics, Seoul National University) ;
  • Jun, Kyoungho (Institute of Molecular Biology and Genetics, Seoul National University) ;
  • Chung, Jongkyeong (Institute of Molecular Biology and Genetics, Seoul National University)
  • Received : 2020.04.07
  • Accepted : 2020.06.24
  • Published : 2020.08.31
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Abstract

While the growth factors like insulin initiate a signaling cascade to induce conformational changes in the mechanistic target of rapamycin complex 1 (mTORC1), amino acids cause the complex to localize to the site of activation, the lysosome. The precise mechanism of how mTORC1 moves in and out of the lysosome is yet to be elucidated in detail. Here we report that microtubules and the motor protein KIF11 are required for the proper dissociation of mTORC1 from the lysosome upon amino acid scarcity. When microtubules are disrupted or KIF11 is knocked down, we observe that mTORC1 localizes to the lysosome even in the amino acid-starved situation where it should be dispersed in the cytosol, causing an elevated mTORC1 activity. Moreover, in the mechanistic perspective, we discover that mTORC1 interacts with KIF11 on the motor domain of KIF11, enabling the complex to move out of the lysosome along microtubules. Our results suggest not only a novel way of the regulation regarding amino acid availability for mTORC1, but also a new role of KIF11 and microtubules in mTOR signaling.

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References

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