Regulation of mTORC1 by the Rag GTPases

Tshering D Lama-Sherpa; Mi-Hyeon Jeong; Jenna L Jewell

doi:10.1042/BST20210038

Regulation of mTORC1 by the Rag GTPases

Biochem Soc Trans. 2023 Apr 26;51(2):655-664. doi: 10.1042/BST20210038.

Authors

Tshering D Lama-Sherpa^#^{1

2

3}, Mi-Hyeon Jeong^#^{1

2

3}, Jenna L Jewell^{1

2

3}

Affiliations

¹ Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, U.S.A.
² Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, U.S.A.
³ Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, U.S.A.

^# Contributed equally.

Abstract

The Rag GTPases are an evolutionarily conserved family that play a crucial role in amino acid sensing by the mammalian target of rapamycin complex 1 (mTORC1). mTORC1 is often referred to as the master regulator of cell growth. mTORC1 hyperactivation is observed in multiple diseases such as cancer, obesity, metabolic disorders, and neurodegeneration. The Rag GTPases sense amino acid levels and form heterodimers, where RagA or RagB binds to RagC or RagD, to recruit mTORC1 to the lysosome where it becomes activated. Here, we review amino acid signaling to mTORC1 through the Rag GTPases.

Keywords: Rag GTPases; amino acid sensing; mTORC1; signaling.

Publication types

Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Amino Acids / metabolism
Lysosomes / metabolism
Mechanistic Target of Rapamycin Complex 1 / metabolism
Monomeric GTP-Binding Proteins* / metabolism
Multiprotein Complexes* / metabolism
Signal Transduction / physiology

Substances

Multiprotein Complexes
Monomeric GTP-Binding Proteins
Mechanistic Target of Rapamycin Complex 1
Amino Acids

Grants and funding

R01 GM129097/GM/NIGMS NIH HHS/United States