論文 - 詳細
| RRC ID | 53493 |
|---|---|
| 著者 | Lohmer LL, Clay MR, Naegeli KM, Chi Q, Ziel JW, Hagedorn EJ, Park JE, Jayadev R, Sherwood DR. |
| タイトル | A Sensitized Screen for Genes Promoting Invadopodia Function In Vivo: CDC-42 and Rab GDI-1 Direct Distinct Aspects of Invadopodia Formation. |
| ジャーナル | PLoS Genet |
| Abstract |
Invadopodia are specialized membrane protrusions composed of F-actin, actin regulators, signaling proteins, and a dynamically trafficked invadopodial membrane that drive cell invasion through basement membrane (BM) barriers in development and cancer. Due to the challenges of studying invasion in vivo, mechanisms controlling invadopodia formation in their native environments remain poorly understood. We performed a sensitized genome-wide RNAi screen and identified 13 potential regulators of invadopodia during anchor cell (AC) invasion into the vulval epithelium in C. elegans. Confirming the specificity of this screen, we identified the Rho GTPase cdc-42, which mediates invadopodia formation in many cancer cell lines. Using live-cell imaging, we show that CDC-42 localizes to the AC-BM interface and is activated by an unidentified vulval signal(s) that induces invasion. CDC-42 is required for the invasive membrane localization of WSP-1 (N-WASP), a CDC-42 effector that promotes polymerization of F-actin. Loss of CDC-42 or WSP-1 resulted in fewer invadopodia and delayed BM breaching. We also characterized a novel invadopodia regulator, gdi-1 (Rab GDP dissociation inhibitor), which mediates membrane trafficking. We show that GDI-1 functions in the AC to promote invadopodia formation. In the absence of GDI-1, the specialized invadopodial membrane was no longer trafficked normally to the invasive membrane, and instead was distributed to plasma membrane throughout the cell. Surprisingly, the pro-invasive signal(s) from the vulval cells also controls GDI-1 activity and invadopodial membrane trafficking. These studies represent the first in vivo screen for genes regulating invadopodia and demonstrate that invadopodia formation requires the integration of distinct cellular processes that are coordinated by an extracellular cue. |
| 巻・号 | 12(1) |
| ページ | e1005786 |
| 公開日 | 2016-1-1 |
| DOI | 10.1371/journal.pgen.1005786 |
| PII | PGENETICS-D-15-01999 |
| PMID | 26765257 |
| PMC | PMC4713207 |
| MeSH | Animals Basement Membrane / growth & development Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans Proteins / biosynthesis Caenorhabditis elegans Proteins / genetics* Cell Cycle Proteins / biosynthesis Cell Cycle Proteins / genetics* Disease Models, Animal Extracellular Matrix / genetics GTP-Binding Proteins / biosynthesis GTP-Binding Proteins / genetics* Gene Expression Regulation, Developmental Guanine Nucleotide Dissociation Inhibitors / biosynthesis Guanine Nucleotide Dissociation Inhibitors / genetics* Humans Neoplasms / genetics* Neoplasms / pathology Podosomes / genetics* Podosomes / pathology Signal Transduction |
| IF | 5.224 |
| 引用数 | 21 |
| 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 | 5 |
| 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 | tm660 |