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Glial cells maintain synapses by inhibiting an activity-dependent retrograde protease signal.
- Source :
-
PLoS genetics [PLoS Genet] 2019 Mar 14; Vol. 15 (3), pp. e1007948. Date of Electronic Publication: 2019 Mar 14 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- Glial cells regulate multiple aspects of synaptogenesis. In the absence of Schwann cells, a peripheral glial cell, motor neurons initially innervate muscle but then degenerate. Here, using a genetic approach, we show that neural activity-regulated negative factors produced by muscle drive neurodegeneration in Schwann cell-deficient mice. We find that thrombin, the hepatic serine protease central to the hemostatic coagulation cascade, is one such negative factor. Trancriptomic analysis shows that expression of the antithrombins serpin C1 and D1 is significantly reduced in Schwann cell-deficient mice. In the absence of peripheral neuromuscular activity, neurodegeneration is completely blocked, and expression of prothrombin in muscle is markedly reduced. In the absence of muscle-derived prothrombin, neurodegeneration is also markedly reduced. Together, these results suggest that Schwann cells regulate NMJs by opposing the effects of activity-regulated, muscle-derived negative factors and provide the first genetic evidence that thrombin plays a central role outside of the coagulation system.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Animals
Gene Expression Profiling
Mice
Motor Neurons metabolism
Motor Neurons pathology
Muscle, Skeletal metabolism
Nerve Degeneration genetics
Neuroglia
Neuromuscular Junction growth & development
Schwann Cells metabolism
Thrombin genetics
Antithrombin III genetics
Heparin Cofactor II genetics
Neuromuscular Junction genetics
Prothrombin genetics
Synapses genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7404
- Volume :
- 15
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- PLoS genetics
- Publication Type :
- Academic Journal
- Accession number :
- 30870413
- Full Text :
- https://doi.org/10.1371/journal.pgen.1007948