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Elife. 2018 May 29;7. pii: e33385. doi: 10.7554/eLife.33385.

Microglial transglutaminase-2 drives myelination and myelin repair via GPR56/ADGRG1 in oligodendrocyte precursor cells.

Author information

1
Division of Newborn Medicine, Department of Medicine, Children's Hospital and Harvard Medical School, Boston, United States.
2
Department of Neurology, F. M. Kirby Neurobiology Center, Children's Hospital and Harvard Medical School, Boston, United States.
3
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
4
Department of Developmental Biology, Washington University School of Medicine, St. Louis, United States.
5
Department of Neural Development and Diseases, Korea Brain Research Institute (KBRI), Daegu, South Korea.
6
Department of Pharmacology, University of Michigan Medical Center, Ann Arbor, United States.

Abstract

In the central nervous system (CNS), myelin formation and repair are regulated by oligodendrocyte (OL) lineage cells, which sense and integrate signals from their environment, including from other glial cells and the extracellular matrix (ECM). The signaling pathways that coordinate this complex communication, however, remain poorly understood. The adhesion G protein-coupled receptor ADGRG1 (also known as GPR56) is an evolutionarily conserved regulator of OL development in humans, mice, and zebrafish, although its activating ligand for OL lineage cells is unknown. Here, we report that microglia-derived transglutaminase-2 (TG2) signals to ADGRG1 on OL precursor cells (OPCs) in the presence of the ECM protein laminin and that TG2/laminin-dependent activation of ADGRG1 promotes OPC proliferation. Signaling by TG2/laminin to ADGRG1 on OPCs additionally improves remyelination in two murine models of demyelination. These findings identify a novel glia-to-glia signaling pathway that promotes myelin formation and repair, and suggest new strategies to enhance remyelination.

KEYWORDS:

microglia; mouse; myelination; neuroscience; oligodendrocyte; remyelination; zebrafish

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