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Elife DOI:10.7554/eLife.33385

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

Publication TypeJournal Article
Year of Publication2018
AuthorsGiera, S, Luo, R, Ying, Y, Ackerman, SD, Jeong, S-J, Stoveken, HM, Folts, CJ, Welsh, CA, Tall, GG, Stevens, B, Monk, KR, Piao, X
JournalElife
Volume7
Date Published2018 05 29
ISSN2050-084X
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.

DOI10.7554/eLife.33385
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/29809138?dopt=Abstract

Alternate JournalElife
PubMed ID29809138
PubMed Central IDPMC5980231
Grant ListR01 NS094164 / NS / NINDS NIH HHS / United States
R56 NS085201 / NS / NINDS NIH HHS / United States
NS094164 / NS / NINDS NIH HHS / United States
R01 GM120110 / GM / NIGMS NIH HHS / United States
NS079445 / NS / NINDS NIH HHS / United States
NS08520 / NS / NINDS NIH HHS / United States
NS085201 / NS / NINDS NIH HHS / United States
NS087801 / NS / NINDS NIH HHS / United States
NS085201 (R56) / NS / NINDS NIH HHS / United States
U54 HD090255 / HD / NICHD NIH HHS / United States
F31 NS087801 / NS / NINDS NIH HHS / United States
R01 NS079445 / NS / NINDS NIH HHS / United States