GATOR2 complex–mediated amino acid signaling regulates brain myelination

Author:

Yu Zongyan123ORCID,Yang Zhiwen23,Ren Guoru23,Wang Yingjie23,Luo Xiang13ORCID,Zhu Feiyan23,Yu Shouyang4,Jia Lanlan4,Chen Mina4,Worley Paul F.5ORCID,Xiao Bo23

Affiliation:

1. School of Life Science and Technology, Harbin Institute of Technology, Harbin 150000, People’s Republic of China

2. Shenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518005, People’s Republic of China

3. Department of Biology, School of Life Sciences, Brain Research Center, Southern University of Science and Technology, Shenzhen 518000, People’s Republic of China

4. Neuroscience & Metabolism Research, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, People’s Republic of China

5. The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205

Abstract

Significance Fast transmission of nerve impulses with energetic efficiency along axons of nerve cells is essential for brain function. Toward this goal, axons are wrapped by the myelin membranes extended from oligodendrocytes, which is known as myelination of axons. Therefore, myelination is dependent on the formation of oligodendrocyte lineage cells. How the oligodendrocyte lineage is formed remains incompletely known. Previous studies suggest that signaling pathways of growth factors and amino acids might coordinate the regulation of oligodendrocyte formation, but the specific amino acid signaling pathway that participates in this regulation has not been identified. This study identifies the amino acid signaling complex GATOR2 (GAP activity towards Rags 2) as a positive regulator of oligodendrocyte formation and myelination that coordinately regulates brain myelination with growth factor signaling.

Funder

National Natural Science Foundation of China

Shenzhen Innovation Committee of Science and Technology

Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions

Shenzhen Key Laboratory of Gene Regulation and Systems Biology

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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