論文 - 詳細
| RRC ID | 54300 |
|---|---|
| 著者 | Shimizu T, Pastuhov SI, Hanafusa H, Matsumoto K, Hisamoto N. |
| タイトル | The C. elegans BRCA2-ALP/Enigma Complex Regulates Axon Regeneration via a Rho GTPase-ROCK-MLC Phosphorylation Pathway. |
| ジャーナル | Cell Rep |
| Abstract |
The ability of specific neurons to regenerate their axons after injury is governed by cell-intrinsic regeneration pathways. However, the mechanisms regulating axon regeneration are not well understood. Here, we identify the brc-2 gene encoding a homolog of the mammalian BRCA2 tumor suppressor as a regulator of axon regeneration in Caenorhabditis elegans motor neurons. We show that the RHO-1/Rho GTPase-LET-502/ROCK (Rho-associated coiled-coil kinase)-regulatory non-muscle myosin light-chain (MLC-4/MLC) phosphorylation signaling pathway regulates axon regeneration. BRC-2 functions between RHO-1 and LET-502, suggesting that BRC-2 is required for the activation of LET-502 by RHO-1-GTP. We also find that one component that interacts with BRC-2, the ALP (α-actinin-associated LIM protein)/Enigma protein ALP-1, is required for regeneration and acts between LET-502 and MLC-4 phosphorylation. Furthermore, we demonstrate that ALP-1 associates with LET-502 and MLC-4. Thus, ALP-1 serves as a platform to activate MLC-4 phosphorylation mediated by the RHO-1-LET-502 signaling pathway. |
| 巻・号 | 24(7) |
| ページ | 1880-1889 |
| 公開日 | 2018-8-14 |
| DOI | 10.1016/j.celrep.2018.07.049 |
| PII | S2211-1247(18)31152-5 |
| PMID | 30110643 |
| MeSH | Adaptor Proteins, Signal Transducing / genetics* Adaptor Proteins, Signal Transducing / metabolism Animals Axotomy / methods Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism DNA-Binding Proteins / genetics* DNA-Binding Proteins / metabolism Gene Expression Regulation LIM Domain Proteins / genetics* LIM Domain Proteins / metabolism Motor Neurons / metabolism Motor Neurons / pathology Myosin Light Chains / genetics* Myosin Light Chains / metabolism Nerve Regeneration / genetics* Neuronal Outgrowth / genetics Neuronal Plasticity / genetics Phosphorylation Protein Binding Signal Transduction rho GTP-Binding Proteins / genetics* rho GTP-Binding Proteins / metabolism rho-Associated Kinases / genetics* rho-Associated Kinases / metabolism |
| IF | 8.109 |
| 引用数 | 4 |
| リソース情報 | |
| 線虫 | tm1086 |