Glial cells maintain synapses by inhibiting an activity-dependent retrograde protease signal.
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 neurodegen...
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doaj-21da27eafb4345da988a4e6b546ea84c2020-11-25T01:28:32ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042019-03-01153e100794810.1371/journal.pgen.1007948Glial cells maintain synapses by inhibiting an activity-dependent retrograde protease signal.Thomas W GouldBertha DominguezFred de WinterGene W YeoPatrick LiuBalaji SundararamanThomas StarkAnthony VuJay L DegenWeichun LinKuo-Fen LeeGlial 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.http://europepmc.org/articles/PMC6417855?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Thomas W Gould Bertha Dominguez Fred de Winter Gene W Yeo Patrick Liu Balaji Sundararaman Thomas Stark Anthony Vu Jay L Degen Weichun Lin Kuo-Fen Lee |
spellingShingle |
Thomas W Gould Bertha Dominguez Fred de Winter Gene W Yeo Patrick Liu Balaji Sundararaman Thomas Stark Anthony Vu Jay L Degen Weichun Lin Kuo-Fen Lee Glial cells maintain synapses by inhibiting an activity-dependent retrograde protease signal. PLoS Genetics |
author_facet |
Thomas W Gould Bertha Dominguez Fred de Winter Gene W Yeo Patrick Liu Balaji Sundararaman Thomas Stark Anthony Vu Jay L Degen Weichun Lin Kuo-Fen Lee |
author_sort |
Thomas W Gould |
title |
Glial cells maintain synapses by inhibiting an activity-dependent retrograde protease signal. |
title_short |
Glial cells maintain synapses by inhibiting an activity-dependent retrograde protease signal. |
title_full |
Glial cells maintain synapses by inhibiting an activity-dependent retrograde protease signal. |
title_fullStr |
Glial cells maintain synapses by inhibiting an activity-dependent retrograde protease signal. |
title_full_unstemmed |
Glial cells maintain synapses by inhibiting an activity-dependent retrograde protease signal. |
title_sort |
glial cells maintain synapses by inhibiting an activity-dependent retrograde protease signal. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2019-03-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC6417855?pdf=render |
work_keys_str_mv |
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