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

Stefanie Giera | Rong Luo | Yanqin Ying | Sarah D Ackerman | Sung-Jin Jeong | Hannah M Stoveken | Christopher J Folts | Christina A Welsh | Gregory G Tall | Beth Stevens | Kelly R Monk | Xianhua Piao
eLife | 2018

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.

Pubmed ID: 29809138

Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: R01 NS094164
  • Agency: NINDS NIH HHS, United States
    Id: R56 NS085201
  • Agency: NINDS NIH HHS, United States
    Id: NS094164
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM120110
  • Agency: NINDS NIH HHS, United States
    Id: NS079445
  • Agency: NINDS NIH HHS, United States
    Id: NS08520
  • Agency: NINDS NIH HHS, United States
    Id: NS085201
  • Agency: NINDS NIH HHS, United States
    Id: NS087801
  • Agency: NINDS NIH HHS, United States
    Id: NS085201 (R56)
  • Agency: NICHD NIH HHS, United States
    Id: U54 HD090255
  • Agency: NINDS NIH HHS, United States
    Id: F31 NS087801
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS079445

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