GATOR2 complex-mediated amino acid signaling regulates brain myelination

Yu, Zongyan1,2,3; Yang, Zhiwen2,3; Ren, Guoru2,3; Wang, Yingjie2,3; Luo, Xiang1,3; Zhu, Feiyan2,3; Yu, Shouyang4,5; Jia, Lanlan4,5; Chen, Mina4,5; Worley, Paul F.6; Xiao, Bo2,3

2022-01-18

10.1073/pnas.2110917119

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   影响因子和分区

0027-8424

1091-6490

Amino acids are essential for cell growth and metabolism. Amino acid and growth factor signaling pathways coordinately regulate the mechanistic target of rapamycin complex 1 (mTORC1) kinase in cell growth and organ development. While major components of amino acid signaling mechanisms have been identified, their biological functions in organ development are unclear. We aimed to understand the functions of the critically positioned amino acid signaling complex GAP activity towards Rags 2 (GATOR2) in brain development. GATOR2 mediates amino acid signaling to mTORC1 by directly linking the amino acid sensors for arginine and leucine to downstream signaling complexes. Now, we report a role of GATOR2 in oligodendrocyte myelination in postnatal brain development. We show that the disruption of GATOR2 complex by genetic deletion of meiosis regulator for oocyte development (Mios, encoding a component of GATOR2) selectively impairs the formation of myelinating oligodendrocytes, thus brain myelination, without apparent effects on the formation of neurons and astrocytes. The loss of Mios impairs cell cycle progression of oligodendrocyte precursor cells, leading to their reduced proliferation and differentiation. Mios deletion manifests a cell type-dependent effect on mTORC1 in the brain, with oligodendroglial mTORC1 selectively affected. However, the role of Mios/GATOR2 in oligodendrocyte formation and myelination involves mTORC1-independent function. This study suggests that GATOR2 coordinates amino acid and growth factor signaling to regulate oligodendrocyte myelination.

myelination oligodendrocytes Mios GATOR2 amino acid signaling

SCI

英语

NI论文

通讯

Shenzhen Innovation Committee of Science and Technology["ZDSYS20200811144002008",2019193984] ; National Natural Science Foundation of China[30800311,31970773,31530042] ; Shenzhen-Hong Kong Institute of Brain ScienceShenzhen Fundamental Research Institutions Grant[2021SHIBS0002]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000748781000002

NATL ACAD SCIENCES

BIOLOGY & BIOCHEMISTRY;CLINICAL MEDICINE;MULTIDISCIPLINARY;PLANT & ANIMAL SCIENCE;ENVIRONMENT/ECOLOGY;SOCIAL SCIENCES, GENERAL;MICROBIOLOGY;ECONOMICS BUSINESS;IMMUNOLOGY;MATERIALS SCIENCE;MATHEMATICS;SPACE SCIENCE;MOLECULAR BIOLOGY & GENETICS;PHARMACOLOGY & TOXICOLOGY;CHEMISTRY;PSYCHIATRY/PSYCHOLOGY;NEUROSCIENCE & BEHAVIOR;PHYSICS;GEOSCIENCES;AGRICULTURAL SCIENCES;ENGINEERING

Web of Science

1.Harbin Inst Technol, Sch Life Sci & Technol, Harbin 150000, Peoples R China
2.Southern Univ Sci & Technol, Sch Life Sci, Shenzhen Key Lab Gene Regulat & Syst Biol, Shenzhen 518005, Peoples R China
3.Southern Univ Sci & Technol, Brain Res Ctr, Sch Life Sci, Dept Biol, Shenzhen 518000, Peoples R China
4.Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Neurosci & Metab Res, Chengdu 610041, Peoples R China
5.Collaborat Innovat Ctr, Chengdu 610041, Peoples R China
6.Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Sch Med, Baltimore, MD 21205 USA

Yu, Zongyan,Yang, Zhiwen,Ren, Guoru,et al. GATOR2 complex-mediated amino acid signaling regulates brain myelination[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2022,119(3).

Yu, Zongyan.,Yang, Zhiwen.,Ren, Guoru.,Wang, Yingjie.,Luo, Xiang.,...&Xiao, Bo.(2022).GATOR2 complex-mediated amino acid signaling regulates brain myelination.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,119(3).

Yu, Zongyan,et al."GATOR2 complex-mediated amino acid signaling regulates brain myelination".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 119.3(2022).