Mislocalization of TORC1 to Lysosomes Caused by KIF11 Inhibition Leads to Aberrant TORC1 Activity

Yoon-Gu Jang1,2, Yujin Choi1,2, Kyoungho Jun1,2

  • 1Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, Korea.

Molecules and Cells
|August 8, 2020
PubMed

Insights

Microtubules and KIF11 motor protein control mTORC1

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Insulin and amino acids regulate mechanistic target of rapamycin complex 1 (mTORC1) signaling.
  • Amino acids induce mTORC1 localization to the lysosome for activation.
  • The precise mechanisms of mTORC1 lysosomal transport remain unclear.

Purpose of the Study:

  • To elucidate the mechanism of mTORC1 dissociation from lysosomes.
  • To investigate the role of microtubules and motor proteins in mTORC1 regulation.
  • To understand how amino acid availability controls mTORC1 activity.

Main Methods:

  • Investigated mTORC1 localization and activity under conditions of amino acid scarcity.
  • Utilized microtubule disruption and KIF11 knockdown experiments.
  • Performed mechanistic studies to identify protein interactions.

Main Results:

  • Microtubules and KIF11 are essential for mTORC1 dissociation from lysosomes during amino acid starvation.
  • Disruption of microtubules or KIF11 knockdown leads to sustained lysosomal localization of mTORC1.
  • mTORC1 interacts with the motor domain of KIF11, facilitating its movement along microtubules.

Conclusions:

  • Identified a novel regulatory mechanism for mTORC1 based on amino acid availability.
  • Demonstrated a new role for KIF11 and microtubules in controlling mTOR signaling.
  • mTORC1 movement from lysosomes is mediated by KIF11-dependent transport along microtubules.

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