The Cell Death Pathway Regulates Synapse Elimination through Cleavage of Gelsolin in Caenorhabditis elegans Neurons
Synapse elimination occurs in development, plasticity, and disease. Although the importance of synapse elimination has been documented in many studies, the molecular mechanisms underlying this process are unclear. Here, using the development of C. elegans RME neurons as a model, we have uncovered a...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-06-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715005677 |
| _version_ | 1818180507222933504 |
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| author | Lingfeng Meng Ben Mulcahy Steven J. Cook Marianna Neubauer Airong Wan Yishi Jin Dong Yan |
| author_facet | Lingfeng Meng Ben Mulcahy Steven J. Cook Marianna Neubauer Airong Wan Yishi Jin Dong Yan |
| author_sort | Lingfeng Meng |
| collection | DOAJ |
| description | Synapse elimination occurs in development, plasticity, and disease. Although the importance of synapse elimination has been documented in many studies, the molecular mechanisms underlying this process are unclear. Here, using the development of C. elegans RME neurons as a model, we have uncovered a function for the apoptosis pathway in synapse elimination. We find that the conserved apoptotic cell death (CED) pathway and axonal mitochondria are required for the elimination of transiently formed clusters of presynaptic components in RME neurons. This function of the CED pathway involves the activation of the actin-filament-severing protein, GSNL-1. Furthermore, we show that caspase CED-3 cleaves GSNL-1 at a conserved C-terminal region and that the cleaved active form of GSNL-1 promotes its actin-severing ability. Our data suggest that activation of the CED pathway contributes to selective elimination of synapses through disassembly of the actin filament network. |
| first_indexed | 2024-12-11T21:20:52Z |
| format | Article |
| id | doaj.art-f455826df838445d8050026a6d08d242 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T21:20:52Z |
| publishDate | 2015-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-f455826df838445d8050026a6d08d2422022-12-22T00:50:29ZengElsevierCell Reports2211-12472015-06-0111111737174810.1016/j.celrep.2015.05.031The Cell Death Pathway Regulates Synapse Elimination through Cleavage of Gelsolin in Caenorhabditis elegans NeuronsLingfeng Meng0Ben Mulcahy1Steven J. Cook2Marianna Neubauer3Airong Wan4Yishi Jin5Dong Yan6Department of Molecular Genetics and Microbiology, Duke University Medical Center, Research Drive, Durham, NC 27710, USALunenfeld-Tanenbaum Research Institute, Toronto, ON M5G 1X5, CanadaDominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Physics and Center for Brain Science, Harvard University, Cambridge, MA 02138, USADepartment of Molecular Genetics and Microbiology, Duke University Medical Center, Research Drive, Durham, NC 27710, USANeurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USADepartment of Molecular Genetics and Microbiology, Duke University Medical Center, Research Drive, Durham, NC 27710, USASynapse elimination occurs in development, plasticity, and disease. Although the importance of synapse elimination has been documented in many studies, the molecular mechanisms underlying this process are unclear. Here, using the development of C. elegans RME neurons as a model, we have uncovered a function for the apoptosis pathway in synapse elimination. We find that the conserved apoptotic cell death (CED) pathway and axonal mitochondria are required for the elimination of transiently formed clusters of presynaptic components in RME neurons. This function of the CED pathway involves the activation of the actin-filament-severing protein, GSNL-1. Furthermore, we show that caspase CED-3 cleaves GSNL-1 at a conserved C-terminal region and that the cleaved active form of GSNL-1 promotes its actin-severing ability. Our data suggest that activation of the CED pathway contributes to selective elimination of synapses through disassembly of the actin filament network.http://www.sciencedirect.com/science/article/pii/S2211124715005677 |
| spellingShingle | Lingfeng Meng Ben Mulcahy Steven J. Cook Marianna Neubauer Airong Wan Yishi Jin Dong Yan The Cell Death Pathway Regulates Synapse Elimination through Cleavage of Gelsolin in Caenorhabditis elegans Neurons Cell Reports |
| title | The Cell Death Pathway Regulates Synapse Elimination through Cleavage of Gelsolin in Caenorhabditis elegans Neurons |
| title_full | The Cell Death Pathway Regulates Synapse Elimination through Cleavage of Gelsolin in Caenorhabditis elegans Neurons |
| title_fullStr | The Cell Death Pathway Regulates Synapse Elimination through Cleavage of Gelsolin in Caenorhabditis elegans Neurons |
| title_full_unstemmed | The Cell Death Pathway Regulates Synapse Elimination through Cleavage of Gelsolin in Caenorhabditis elegans Neurons |
| title_short | The Cell Death Pathway Regulates Synapse Elimination through Cleavage of Gelsolin in Caenorhabditis elegans Neurons |
| title_sort | cell death pathway regulates synapse elimination through cleavage of gelsolin in caenorhabditis elegans neurons |
| url | http://www.sciencedirect.com/science/article/pii/S2211124715005677 |
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