A MIG-15/JNK-1 MAP kinase cascade opposes RPM-1 signaling in synapse formation and learning.
The Pam/Highwire/RPM-1 (PHR) proteins are conserved intracellular signaling hubs that regulate synapse formation and axon termination. The C. elegans PHR protein, called RPM-1, acts as a ubiquitin ligase to inhibit the DLK-1 and MLK-1 MAP kinase pathways. We have identified several kinases that are...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-12-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC5754208?pdf=render |
| _version_ | 1828383648510902272 |
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| author | Oliver Crawley Andrew C Giles Muriel Desbois Sudhanva Kashyap Rayna Birnbaum Brock Grill |
| author_facet | Oliver Crawley Andrew C Giles Muriel Desbois Sudhanva Kashyap Rayna Birnbaum Brock Grill |
| author_sort | Oliver Crawley |
| collection | DOAJ |
| description | The Pam/Highwire/RPM-1 (PHR) proteins are conserved intracellular signaling hubs that regulate synapse formation and axon termination. The C. elegans PHR protein, called RPM-1, acts as a ubiquitin ligase to inhibit the DLK-1 and MLK-1 MAP kinase pathways. We have identified several kinases that are likely to form a new MAP kinase pathway that suppresses synapse formation defects, but not axon termination defects, in the mechanosensory neurons of rpm-1 mutants. This pathway includes: MIG-15 (MAP4K), NSY-1 (MAP3K), JKK-1 (MAP2K) and JNK-1 (MAPK). Transgenic overexpression of kinases in the MIG-15/JNK-1 pathway is sufficient to impair synapse formation in wild-type animals. The MIG-15/JNK-1 pathway functions cell autonomously in the mechanosensory neurons, and these kinases localize to presynaptic terminals providing further evidence of a role in synapse development. Loss of MIG-15/JNK-1 signaling also suppresses defects in habituation to repeated mechanical stimuli in rpm-1 mutants, a behavioral deficit that is likely to arise from impaired glutamatergic synapse formation. Interestingly, habituation results are consistent with the MIG-15/JNK-1 pathway functioning as a parallel opposing pathway to RPM-1. These findings indicate the MIG-15/JNK-1 pathway can restrict both glutamatergic synapse formation and short-term learning. |
| first_indexed | 2024-12-10T04:52:46Z |
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| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-10T04:52:46Z |
| publishDate | 2017-12-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Genetics |
| spelling | doaj.art-cfb9010cb6b946d1a98edb69e94d5cf02022-12-22T02:01:35ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042017-12-011312e100709510.1371/journal.pgen.1007095A MIG-15/JNK-1 MAP kinase cascade opposes RPM-1 signaling in synapse formation and learning.Oliver CrawleyAndrew C GilesMuriel DesboisSudhanva KashyapRayna BirnbaumBrock GrillThe Pam/Highwire/RPM-1 (PHR) proteins are conserved intracellular signaling hubs that regulate synapse formation and axon termination. The C. elegans PHR protein, called RPM-1, acts as a ubiquitin ligase to inhibit the DLK-1 and MLK-1 MAP kinase pathways. We have identified several kinases that are likely to form a new MAP kinase pathway that suppresses synapse formation defects, but not axon termination defects, in the mechanosensory neurons of rpm-1 mutants. This pathway includes: MIG-15 (MAP4K), NSY-1 (MAP3K), JKK-1 (MAP2K) and JNK-1 (MAPK). Transgenic overexpression of kinases in the MIG-15/JNK-1 pathway is sufficient to impair synapse formation in wild-type animals. The MIG-15/JNK-1 pathway functions cell autonomously in the mechanosensory neurons, and these kinases localize to presynaptic terminals providing further evidence of a role in synapse development. Loss of MIG-15/JNK-1 signaling also suppresses defects in habituation to repeated mechanical stimuli in rpm-1 mutants, a behavioral deficit that is likely to arise from impaired glutamatergic synapse formation. Interestingly, habituation results are consistent with the MIG-15/JNK-1 pathway functioning as a parallel opposing pathway to RPM-1. These findings indicate the MIG-15/JNK-1 pathway can restrict both glutamatergic synapse formation and short-term learning.http://europepmc.org/articles/PMC5754208?pdf=render |
| spellingShingle | Oliver Crawley Andrew C Giles Muriel Desbois Sudhanva Kashyap Rayna Birnbaum Brock Grill A MIG-15/JNK-1 MAP kinase cascade opposes RPM-1 signaling in synapse formation and learning. PLoS Genetics |
| title | A MIG-15/JNK-1 MAP kinase cascade opposes RPM-1 signaling in synapse formation and learning. |
| title_full | A MIG-15/JNK-1 MAP kinase cascade opposes RPM-1 signaling in synapse formation and learning. |
| title_fullStr | A MIG-15/JNK-1 MAP kinase cascade opposes RPM-1 signaling in synapse formation and learning. |
| title_full_unstemmed | A MIG-15/JNK-1 MAP kinase cascade opposes RPM-1 signaling in synapse formation and learning. |
| title_short | A MIG-15/JNK-1 MAP kinase cascade opposes RPM-1 signaling in synapse formation and learning. |
| title_sort | mig 15 jnk 1 map kinase cascade opposes rpm 1 signaling in synapse formation and learning |
| url | http://europepmc.org/articles/PMC5754208?pdf=render |
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