Microglial transglutaminase-2 drives myelination and myelin repair via GPR56/ADGRG1 in oligodendrocyte precursor cells
| Autor: | Rong Luo, Yanqin Ying, Christina A. Welsh, Sarah D. Ackerman, Beth Stevens, Sung Jin Jeong, Gregory G. Tall, Hannah M. Stoveken, Kelly R. Monk, Christopher J. Folts, Stefanie Giera, Xianhua Piao |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Receptor Platelet-Derived Growth Factor alpha Mouse microglia Receptors G-Protein-Coupled Extracellular matrix Myelin Mice Cerebellum Biology (General) Zebrafish Mice Knockout Microglia Chemistry General Neuroscience myelination Gene Expression Regulation Developmental Cell Differentiation General Medicine Cell biology Oligodendroglia medicine.anatomical_structure Medicine Female Signal transduction Research Article Signal Transduction QH301-705.5 Science Neurogenesis CX3C Chemokine Receptor 1 General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Prosencephalon GTP-Binding Proteins Precursor cell medicine Animals Humans Cell Lineage Protein Glutamine gamma Glutamyltransferase 2 Remyelination Oligodendrocyte Precursor Cells Transglutaminases General Immunology and Microbiology Oligodendrocyte 030104 developmental biology GPR56 remyelination nervous system Laminin oligodendrocyte Neuroscience Demyelinating Diseases |
| Zdroj: | eLife eLife, Vol 7 (2018) |
| ISSN: | 2050-084X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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