Leucyl-tRNA Synthetase Activates Vps34 in Amino Acid-Sensing mTORC1 Signaling

Mee Sup Yoon, Kook Son, Edwin Arauz, Jung Min Han, Sunghoon Kim, Jie Chen

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Amino acid availability activates signaling by the mammalian target of rapamycin (mTOR) complex 1, mTORC1, a master regulator of cell growth. The class III PI-3-kinase Vps34 mediates amino acid signaling to mTORC1 by regulating lysosomal translocation and activation of the phospholipase PLD1. Here, we identify leucyl-tRNA synthetase (LRS) as a leucine sensor for the activation of Vps34-PLD1 upstream of mTORC1. LRS is necessary for amino acid-induced Vps34 activation, cellular PI(3)P level increase, PLD1 activation, and PLD1 lysosomal translocation. Leucine binding, but not tRNA charging activity of LRS, is required for this regulation. Moreover, LRS physically interacts with Vps34 in amino acid-stimulatable non-autophagic complexes. Finally, purified LRS protein activates Vps34 kinase in vitro in a leucine-dependent manner. Collectively, our findings provide compelling evidence for a direct role of LRS in amino acid activation of Vps34 via a non-canonical mechanism and fill a gap in the amino acid-sensing mTORC1 signaling network.

Original languageEnglish
Pages (from-to)1510-1517
Number of pages8
JournalCell Reports
Volume16
Issue number6
DOIs
Publication statusPublished - 2016 Aug 9

Fingerprint

Amino Acyl-tRNA Synthetases
Amino Acids
Chemical activation
Leucine
Transfer RNA Aminoacylation
Aminoacylation
Phospholipases
Cell growth
Transfer RNA
Phosphatidylinositol 3-Kinases
mechanistic target of rapamycin complex 1
Phosphotransferases
Availability
Growth
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Yoon, Mee Sup ; Son, Kook ; Arauz, Edwin ; Han, Jung Min ; Kim, Sunghoon ; Chen, Jie. / Leucyl-tRNA Synthetase Activates Vps34 in Amino Acid-Sensing mTORC1 Signaling. In: Cell Reports. 2016 ; Vol. 16, No. 6. pp. 1510-1517.
@article{7216d082604b46ca8bfb8a949b448c5a,
title = "Leucyl-tRNA Synthetase Activates Vps34 in Amino Acid-Sensing mTORC1 Signaling",
abstract = "Amino acid availability activates signaling by the mammalian target of rapamycin (mTOR) complex 1, mTORC1, a master regulator of cell growth. The class III PI-3-kinase Vps34 mediates amino acid signaling to mTORC1 by regulating lysosomal translocation and activation of the phospholipase PLD1. Here, we identify leucyl-tRNA synthetase (LRS) as a leucine sensor for the activation of Vps34-PLD1 upstream of mTORC1. LRS is necessary for amino acid-induced Vps34 activation, cellular PI(3)P level increase, PLD1 activation, and PLD1 lysosomal translocation. Leucine binding, but not tRNA charging activity of LRS, is required for this regulation. Moreover, LRS physically interacts with Vps34 in amino acid-stimulatable non-autophagic complexes. Finally, purified LRS protein activates Vps34 kinase in vitro in a leucine-dependent manner. Collectively, our findings provide compelling evidence for a direct role of LRS in amino acid activation of Vps34 via a non-canonical mechanism and fill a gap in the amino acid-sensing mTORC1 signaling network.",
author = "Yoon, {Mee Sup} and Kook Son and Edwin Arauz and Han, {Jung Min} and Sunghoon Kim and Jie Chen",
year = "2016",
month = "8",
day = "9",
doi = "10.1016/j.celrep.2016.07.008",
language = "English",
volume = "16",
pages = "1510--1517",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "6",

}

Leucyl-tRNA Synthetase Activates Vps34 in Amino Acid-Sensing mTORC1 Signaling. / Yoon, Mee Sup; Son, Kook; Arauz, Edwin; Han, Jung Min; Kim, Sunghoon; Chen, Jie.

In: Cell Reports, Vol. 16, No. 6, 09.08.2016, p. 1510-1517.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Leucyl-tRNA Synthetase Activates Vps34 in Amino Acid-Sensing mTORC1 Signaling

AU - Yoon, Mee Sup

AU - Son, Kook

AU - Arauz, Edwin

AU - Han, Jung Min

AU - Kim, Sunghoon

AU - Chen, Jie

PY - 2016/8/9

Y1 - 2016/8/9

N2 - Amino acid availability activates signaling by the mammalian target of rapamycin (mTOR) complex 1, mTORC1, a master regulator of cell growth. The class III PI-3-kinase Vps34 mediates amino acid signaling to mTORC1 by regulating lysosomal translocation and activation of the phospholipase PLD1. Here, we identify leucyl-tRNA synthetase (LRS) as a leucine sensor for the activation of Vps34-PLD1 upstream of mTORC1. LRS is necessary for amino acid-induced Vps34 activation, cellular PI(3)P level increase, PLD1 activation, and PLD1 lysosomal translocation. Leucine binding, but not tRNA charging activity of LRS, is required for this regulation. Moreover, LRS physically interacts with Vps34 in amino acid-stimulatable non-autophagic complexes. Finally, purified LRS protein activates Vps34 kinase in vitro in a leucine-dependent manner. Collectively, our findings provide compelling evidence for a direct role of LRS in amino acid activation of Vps34 via a non-canonical mechanism and fill a gap in the amino acid-sensing mTORC1 signaling network.

AB - Amino acid availability activates signaling by the mammalian target of rapamycin (mTOR) complex 1, mTORC1, a master regulator of cell growth. The class III PI-3-kinase Vps34 mediates amino acid signaling to mTORC1 by regulating lysosomal translocation and activation of the phospholipase PLD1. Here, we identify leucyl-tRNA synthetase (LRS) as a leucine sensor for the activation of Vps34-PLD1 upstream of mTORC1. LRS is necessary for amino acid-induced Vps34 activation, cellular PI(3)P level increase, PLD1 activation, and PLD1 lysosomal translocation. Leucine binding, but not tRNA charging activity of LRS, is required for this regulation. Moreover, LRS physically interacts with Vps34 in amino acid-stimulatable non-autophagic complexes. Finally, purified LRS protein activates Vps34 kinase in vitro in a leucine-dependent manner. Collectively, our findings provide compelling evidence for a direct role of LRS in amino acid activation of Vps34 via a non-canonical mechanism and fill a gap in the amino acid-sensing mTORC1 signaling network.

UR - http://www.scopus.com/inward/record.url?scp=84979783281&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84979783281&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2016.07.008

DO - 10.1016/j.celrep.2016.07.008

M3 - Article

VL - 16

SP - 1510

EP - 1517

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 6

ER -