Amino Acid Sensing bymTORC1: Intracellular Transporters Mark the Spot

被引：231

作者：

Goberdhan, Deborah C. I. ^{[1
]}

Wilson, Clive ^{[1
]}

Harris, Adrian L. ^{[2
]}

机构：

[1] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England

[2] Univ Oxford, Weatherall Inst Mol Med, Oxford OX3 9DS, England

来源：

CELL METABOLISM | 2016年 / 23卷 / 04期

基金：

英国生物技术与生命科学研究理事会; 英国惠康基金; 英国医学研究理事会;

关键词：

TUMOR-SUPPRESSOR; RAG GTPASES; LYSOSOMAL RECRUITMENT; MAMMALIAN TARGET; REGULATES MTORC1; LEUCINE SENSOR; CELL-GROWTH; COMPLEX; RAPAMYCIN; ACTIVATION;

D O I：

10.1016/j.cmet.2016.03.013

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Cell metabolism and growth are matched to nutrient availability via the amino-acid-regulated mechanistic target of rapamycin complex 1 (mTORC1). Transporters have emerged as important amino acid sensors controlling mTOR recruitment and activation at the surface of multiple intracellular compartments. Classically, this has involved late endosomes and lysosomes, but now, in a recent twist, also the Golgi apparatus. Here we propose a model in which specific amino acids in assorted compartments activate different mTORC1 complexes, which may have distinct drug sensitivities and functions. We will discuss the implications of this for mTORC1 function in health and disease.

引用

页码：580 / 589

页数：10

共 78 条

[1]

Requirement for lysosomal localization of mTOR for its activation differs between leucine and other amino acids [J].

Averous, Julien ;

Lambert-Langlais, Sarah ;

Carraro, Valerie ;

Gourbeyre, Ophelie ;

Parry, Laurent ;

B'Chir, Wafa ;

Muranishi, Yuki ;

Jousse, Celine ;

Bruhat, Alain ;

Maurin, Anne-Catherine ;

Proud, Christopher G. ;

Fafournoux, Pierre .

CELLULAR SIGNALLING, 2014, 26 (09) :1918-1927

[2]

Regulation of mTORC1 by amino acids [J].

Bar-Peled, Liron ;

Sabatini, David M. .

TRENDS IN CELL BIOLOGY, 2014, 24 (07) :400-406

[3]

A Tumor Suppressor Complex with GAP Activity for the Rag GTPases That Signal Amino Acid Sufficiency to mTORC1 [J].

Bar-Peled, Liron ;

Chantranupong, Lynne ;

Cherniack, Andrew D. ;

Chen, Walter W. ;

Ottina, Kathleen A. ;

Grabiner, Brian C. ;

Spear, Eric D. ;

Carter, Scott L. ;

Meyerson, Matthew ;

Sabatini, David M. .

SCIENCE, 2013, 340 (6136) :1100-1106

[4]

Regulation of targets of mTOR (mammalian target of rapamycin) signalling by intracellular amino acid availability [J].

Beugnet, A ;

Tee, AR ;

Taylor, PM ;

Proud, CG .

BIOCHEMICAL JOURNAL, 2003, 372 :555-566

[5]

Functional characterization of two novel mammalian electrogenic proton-dependent amino acid cotransporters [J].

Boll, M ;

Foltz, MT ;

Rubio-Aliaga, I ;

Kottra, G ;

Daniel, H .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (25) :22966-22973

[6]

Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex [J].

Brugarolas, J ;

Lei, K ;

Hurley, RL ;

Manning, BD ;

Reiling, JH ;

Hafen, E ;

Witter, LA ;

Ellisen, LW ;

Kaelin, WG .

GENES & DEVELOPMENT, 2004, 18 (23) :2893-2904

[7]

MAP4K3 regulates body size and metabolism in Drosophila [J].

Bryk, Boris ;

Hahn, Katrin ;

Cohen, Stephen M. ;

Teleman, Aurelio A. .

DEVELOPMENTAL BIOLOGY, 2010, 344 (01) :150-157

[8]

hVps34 is a nutrient-regulated lipid kinase required for activation of p70 S6 kinase [J].

Byfield, MP ;

Murray, JT ;

Backer, JM .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (38) :33076-33082

[9]

Control of TSC2-Rheb signaling axis by arginine regulates mTORC1 activity [J].

Carroll, Bernadette ;

Maetzel, Dorothea ;

Maddocks, Oliver D. K. ;

Otten, Gisela ;

Ratcliff, Matthew ;

Smith, Graham R. ;

Dunlop, Elaine A. ;

Passos, Joao F. ;

Davies, Owen R. ;

Jaenisch, Rudolf ;

Tee, Andrew R. ;

Sarkar, Sovan ;

Korolchuk, Viktor I. .

ELIFE, 2016, 5

[10]

Amino acids and autophagy: cross-talk and co-operation to control cellular homeostasis [J].

Carroll, Bernadette ;

Korolchuk, Viktor I. ;

Sarkar, Sovan .

AMINO ACIDS, 2015, 47 (10) :2065-2088

← 1 2 3 4 5 6 7 8 →