論文 - 詳細
| RRC ID | 53260 |
|---|---|
| 著者 | D'Souza SA, Rajendran L, Bagg R, Barbier L, van Pel DM, Moshiri H, Roy PJ. |
| タイトル | The MADD-3 LAMMER Kinase Interacts with a p38 MAP Kinase Pathway to Regulate the Display of the EVA-1 Guidance Receptor in Caenorhabditis elegans. |
| ジャーナル | PLoS Genet |
| Abstract |
The proper display of transmembrane receptors on the leading edge of migrating cells and cell extensions is essential for their response to guidance cues. We previously discovered that MADD-4, which is an ADAMTSL secreted by motor neurons in Caenorhabditis elegans, interacts with an UNC-40/EVA-1 co-receptor complex on muscles to attract plasma membrane extensions called muscle arms. In nematodes, the muscle arm termini harbor the post-synaptic elements of the neuromuscular junction. Through a forward genetic screen for mutants with disrupted muscle arm extension, we discovered that a LAMMER kinase, which we call MADD-3, is required for the proper display of the EVA-1 receptor on the muscle's plasma membrane. Without MADD-3, EVA-1 levels decrease concomitantly with a reduction of the late-endosomal marker RAB-7. Through a genetic suppressor screen, we found that the levels of EVA-1 and RAB-7 can be restored in madd-3 mutants by eliminating the function of a p38 MAP kinase pathway. We also found that EVA-1 and RAB-7 will accumulate in madd-3 mutants upon disrupting CUP-5, which is a mucolipin ortholog required for proper lysosome function. Together, our data suggests that the MADD-3 LAMMER kinase antagonizes the p38-mediated endosomal trafficking of EVA-1 to the lysosome. In this way, MADD-3 ensures that sufficient levels of EVA-1 are present to guide muscle arm extension towards the source of the MADD-4 guidance cue. |
| 巻・号 | 12(4) |
| ページ | e1006010 |
| 公開日 | 2016-4-1 |
| DOI | 10.1371/journal.pgen.1006010 |
| PII | PGENETICS-D-15-02190 |
| PMID | 27123983 |
| PMC | PMC4849719 |
| MeSH | Animals Caenorhabditis elegans / enzymology Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Carrier Proteins / metabolism* Cell Adhesion Molecules / metabolism Gene Expression Regulation, Developmental Intracellular Signaling Peptides and Proteins / metabolism Lysosomes / metabolism MAP Kinase Signaling System Membrane Proteins / metabolism Nerve Tissue Proteins / metabolism Netrins Neuromuscular Junction / physiology Protein Transport / physiology p38 Mitogen-Activated Protein Kinases / genetics p38 Mitogen-Activated Protein Kinases / metabolism* rab GTP-Binding Proteins / metabolism* |
| IF | 5.175 |
| 引用数 | 5 |
| 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 | 8 |
| 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 | tm4024 tm807 |