期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2110917119
关键词
myelination; oligodendrocytes; Mios; GATOR2; amino acid signaling
资金
- 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]
GATOR2 plays a crucial role in the formation of myelin sheath in brain development, by regulating the signaling of amino acids and growth factors to mTORC1. Disruption of GATOR2 impairs the proliferation and differentiation of oligodendrocyte precursor cells, leading to defective myelination in the brain.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据