論文 - 詳細
| RRC ID | 59508 |
|---|---|
| 著者 | Hisamoto N, Shimizu T, Asai K, Sakai Y, Pastuhov SI, Hanafusa H, Matsumoto K. |
| タイトル | C. elegans Tensin Promotes Axon Regeneration by Linking the Met-like SVH-2 and Integrin Signaling Pathways. |
| ジャーナル | J Neurosci |
| Abstract |
Axon regeneration is a conserved mechanism induced by axon injury that initiates a neuronal response leading to regrowth of the axon. In Caenorhabditis elegans, the initiation of axon regeneration is regulated by the JNK MAP kinase (MAPK) pathway. We have previously identified a number of genes affecting the JNK pathway using an RNAi-based screen. Analysis of these genes, called the svh genes, has shed new light on the regulation of axon regeneration, revealing the involvement of a signaling cascade consisting of a growth factor SVH-1 and its receptor, the tyrosine kinase SVH-2. Here, we characterize the svh-6/tns-1 gene, which is a homolog of mammalian tensin, and show that it is a positive regulator of axon regeneration in motor neurons. We demonstrate that TNS-1 interacts with tyrosine-autophosphorylated SVH-2 and the integrin β subunit PAT-3 via its SH2 and PTB domains, respectively, to promote axon regeneration. These results suggest that TNS-1 acts as an adaptor to link the SVH-2 and integrin signaling pathways.SIGNIFICANCE STATEMENT The Caenorhabditis elegans JNK MAPK pathway regulates the initiation of axon regeneration. Previously, we showed that a signaling cascade consisting of the HGF-like growth factor SVH-1 and its Met-like receptor tyrosine kinase SVH-2 promotes axon regeneration through activation of the JNK pathway. In this study, we show that the C. elegans tensin, TNS-1, is required for efficient regeneration after axon injury. Phosphorylation of SVH-2 on tyrosine mediates its interaction with the SH2 domain of TNS-1 to positively regulate axon regeneration. Furthermore, TNS-1 interacts via its PTB domain with the integrin β subunit PAT-3. These results suggest that TNS-1 plays a critical role in the regulation of axon regeneration by linking the SVH-2 and integrin signaling pathways. |
| 巻・号 | 39(29) |
| ページ | 5662-5672 |
| 公開日 | 2019-7-17 |
| DOI | 10.1523/JNEUROSCI.2059-18.2019 |
| PII | JNEUROSCI.2059-18.2019 |
| PMID | 31109965 |
| PMC | PMC6636086 |
| MeSH | Amino Acid Sequence Animals Animals, Genetically Modified Axons / physiology* COS Cells Caenorhabditis elegans Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Chlorocebus aethiops Methionine / genetics Methionine / metabolism Nerve Regeneration / physiology* Receptor Protein-Tyrosine Kinases / genetics Receptor Protein-Tyrosine Kinases / metabolism* Signal Transduction / physiology Tensins / genetics Tensins / metabolism* |
| IF | 6.074 |
| 引用数 | 3 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 10 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm737 |