Leucine-induced localization of Leucyl-tRNA synthetase in lysosome membrane

Hyosun Choi, Jung Bae Son, Jooyoun Kang, Jiwoong Kwon, Jong Hyun Kim, Minkyo Jung, Seong Keun Kim, Sunghoon Kim, Ji Young Mun

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Leucyl-tRNA synthetase (LRS) plays major roles in providing leucine-tRNA and activating mechanistic target of rapamycin complex 1 (mTORC1) through intracellular leucine sensing. mTORC1 activated by amino acids affects the influence on physiology functions including cell proliferation, protein synthesis and autophagy in various organisms. Biochemical results demonstrating leucine sensing have been published, but visual results are lacking. Therefore, we observed the location of LRS with and without leucine using stimulated emission depletion (STED) microscopy one of the super-resolution microscopy and transmission electron microscopy (TEM). This revealed that LRS was translocated to the lysosome on addition of leucine. The translocation was inhibited by treatment with compound BC-LI-0186, disrupting the interaction between RagD and LRS. Immuno-TEM revealed a clear decrease in LRS translocation to the lysosome on addition of the inhibitor. This direct visualization of leucine sensing and LRS translocation to the lysosome was related to mTORC1 activation. To study the relationship between mTORC1 activation and LRS translocation, we monitored the change in autophagy for each condition using TEM and CLSM. The results showed a decrease in autophagy on addition of leucine, demonstrating crosstalk between leucine sensing, LRS translocation, RagD interaction, and mTORC1 activation.

Original languageEnglish
Pages (from-to)1129-1135
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume493
Issue number2
DOIs
Publication statusPublished - 2017 Nov 18

Bibliographical note

Funding Information:
These works were supported by Global Frontier Research Grant ( NRF-2014M3A6A4075063 , NRF-2015M3A6A4065729 ) and the Basic Science Research Program ( NRF-2015R1C1A1A02037153 ).

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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