論文 - 詳細
| RRC ID | 46288 |
|---|---|
| 著者 | Mohamed AM, Boudreau JR, Yu FP, Liu J, Chin-Sang ID. |
| タイトル | The Caenorhabditis elegans Eph receptor activates NCK and N-WASP, and inhibits Ena/VASP to regulate growth cone dynamics during axon guidance. |
| ジャーナル | PLoS Genet |
| Abstract |
The Eph receptor tyrosine kinases (RTKs) are regulators of cell migration and axon guidance. However, our understanding of the molecular mechanisms by which Eph RTKs regulate these processes is still incomplete. To understand how Eph receptors regulate axon guidance in Caenorhabditis elegans, we screened for suppressors of axon guidance defects caused by a hyperactive VAB-1/Eph RTK. We identified NCK-1 and WSP-1/N-WASP as downstream effectors of VAB-1. Furthermore, VAB-1, NCK-1, and WSP-1 can form a complex in vitro. We also report that NCK-1 can physically bind UNC-34/Enabled (Ena), and suggest that VAB-1 inhibits the NCK-1/UNC-34 complex and negatively regulates UNC-34. Our results provide a model of the molecular events that allow the VAB-1 RTK to regulate actin dynamics for axon guidance. We suggest that VAB-1/Eph RTK can stop axonal outgrowth by inhibiting filopodia formation at the growth cone by activating Arp2/3 through a VAB-1/NCK-1/WSP-1 complex and by inhibiting UNC-34/Ena activity. |
| 巻・号 | 8(2) |
| ページ | e1002513 |
| 公開日 | 2012-1-1 |
| DOI | 10.1371/journal.pgen.1002513 |
| PII | PGENETICS-D-11-01183 |
| PMID | 22383893 |
| PMC | PMC3285579 |
| MeSH | Actins / physiology Adaptor Proteins, Signal Transducing / genetics Adaptor Proteins, Signal Transducing / metabolism Animals Animals, Genetically Modified Caenorhabditis elegans / cytology Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Adhesion Molecules / genetics Cell Adhesion Molecules / metabolism Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* Cytoskeleton / physiology* Growth Cones / physiology* Growth Cones / ultrastructure Microfilament Proteins / genetics Microfilament Proteins / metabolism Neurons / physiology Neurons / ultrastructure Oncogene Proteins / genetics Oncogene Proteins / metabolism Phosphoproteins / genetics Phosphoproteins / metabolism Receptor Protein-Tyrosine Kinases / genetics Receptor Protein-Tyrosine Kinases / metabolism* Signal Transduction* |
| IF | 5.175 |
| 引用数 | 22 |
| WOS 分野 | GENETICS & HEREDITY |
| リソース情報 | |
| 線虫 | tm2299 |