Motor neuron activity enhances the proteomic stress caused by autophagy defects in the target muscle.
Several lines of evidence demonstrate that increased neuronal excitability can enhance proteomic stress. For example, epilepsy can enhance the proteomic stress caused by the expression of certain aggregation-prone proteins implicated in neurodegeneration. However, unanswered questions remain concern...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0291477&type=printable |
| _version_ | 1797315926138290176 |
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| author | Saurabh Srivastav Kevin van der Graaf Prisha C Jonnalagadda Maanvi Thawani James A McNew Michael Stern |
| author_facet | Saurabh Srivastav Kevin van der Graaf Prisha C Jonnalagadda Maanvi Thawani James A McNew Michael Stern |
| author_sort | Saurabh Srivastav |
| collection | DOAJ |
| description | Several lines of evidence demonstrate that increased neuronal excitability can enhance proteomic stress. For example, epilepsy can enhance the proteomic stress caused by the expression of certain aggregation-prone proteins implicated in neurodegeneration. However, unanswered questions remain concerning the mechanisms by which increased neuronal excitability accomplishes this enhancement. Here we test whether increasing neuronal excitability at a particular identified glutamatergic synapse, the Drosophila larval neuromuscular junction, can enhance the proteomic stress caused by mutations in the ER fusion/GTPase gene atlastin (atl). It was previously shown that larval muscle from the atl2 null mutant is defective in autophagy and accumulates protein aggregates containing ubiquitin (poly-UB aggregates). To determine if increased neuronal excitability might enhance the increased proteomic stress caused by atl2, we activated the TrpA1-encoded excitability channel within neurons. We found that TrpA1 activation had no effect on poly-UB aggregate accumulation in wildtype muscle, but significantly increased poly-UB aggregate number in atl2 muscle. Previous work has shown that atl loss from either neuron or muscle increases muscle poly-UB aggregate number. We found that neuronal TrpA1 activation enhanced poly-UB aggregate number when atl was removed from muscle, but not from neuron. Neuronal TrpA1 activation enhanced other phenotypes conferred by muscle atl loss, such as decreased pupal size and decreased viability. Taken together, these results indicate that the proteomic stress caused by muscle atl loss is enhanced by increasing neuronal excitability. |
| first_indexed | 2024-03-08T03:10:56Z |
| format | Article |
| id | doaj.art-91e690ee724b46f59c32d2f564cfa684 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-08T03:10:56Z |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-91e690ee724b46f59c32d2f564cfa6842024-02-13T05:34:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01191e029147710.1371/journal.pone.0291477Motor neuron activity enhances the proteomic stress caused by autophagy defects in the target muscle.Saurabh SrivastavKevin van der GraafPrisha C JonnalagaddaMaanvi ThawaniJames A McNewMichael SternSeveral lines of evidence demonstrate that increased neuronal excitability can enhance proteomic stress. For example, epilepsy can enhance the proteomic stress caused by the expression of certain aggregation-prone proteins implicated in neurodegeneration. However, unanswered questions remain concerning the mechanisms by which increased neuronal excitability accomplishes this enhancement. Here we test whether increasing neuronal excitability at a particular identified glutamatergic synapse, the Drosophila larval neuromuscular junction, can enhance the proteomic stress caused by mutations in the ER fusion/GTPase gene atlastin (atl). It was previously shown that larval muscle from the atl2 null mutant is defective in autophagy and accumulates protein aggregates containing ubiquitin (poly-UB aggregates). To determine if increased neuronal excitability might enhance the increased proteomic stress caused by atl2, we activated the TrpA1-encoded excitability channel within neurons. We found that TrpA1 activation had no effect on poly-UB aggregate accumulation in wildtype muscle, but significantly increased poly-UB aggregate number in atl2 muscle. Previous work has shown that atl loss from either neuron or muscle increases muscle poly-UB aggregate number. We found that neuronal TrpA1 activation enhanced poly-UB aggregate number when atl was removed from muscle, but not from neuron. Neuronal TrpA1 activation enhanced other phenotypes conferred by muscle atl loss, such as decreased pupal size and decreased viability. Taken together, these results indicate that the proteomic stress caused by muscle atl loss is enhanced by increasing neuronal excitability.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0291477&type=printable |
| spellingShingle | Saurabh Srivastav Kevin van der Graaf Prisha C Jonnalagadda Maanvi Thawani James A McNew Michael Stern Motor neuron activity enhances the proteomic stress caused by autophagy defects in the target muscle. PLoS ONE |
| title | Motor neuron activity enhances the proteomic stress caused by autophagy defects in the target muscle. |
| title_full | Motor neuron activity enhances the proteomic stress caused by autophagy defects in the target muscle. |
| title_fullStr | Motor neuron activity enhances the proteomic stress caused by autophagy defects in the target muscle. |
| title_full_unstemmed | Motor neuron activity enhances the proteomic stress caused by autophagy defects in the target muscle. |
| title_short | Motor neuron activity enhances the proteomic stress caused by autophagy defects in the target muscle. |
| title_sort | motor neuron activity enhances the proteomic stress caused by autophagy defects in the target muscle |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0291477&type=printable |
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