論文 - 詳細
| RRC ID | 34497 |
|---|---|
| 著者 | Obata F, Tanaka S, Kashio S, Tsujimura H, Sato R, Miura M. |
| タイトル | Induction of rapid and selective cell necrosis in Drosophila using Bacillus thuringiensis Cry toxin and its silkworm receptor. |
| ジャーナル | BMC Biol |
| Abstract |
BACKGROUND:Genetic ablation of target cells is a powerful tool to study the origins and functions of cells, tissue regeneration, or pathophysiology in a human disease model in vivo. Several methods for selective cell ablation by inducing apoptosis have been established, using exogenous toxins or endogenous proapoptotic genes. However, their application is limited to cells with intact apoptotic machinery. RESULTS:Herein, we established a method for inducing rapid and selective cell necrosis by the pore-forming bacterial toxin Cry1Aa, which is specifically active in cells expressing the Cry1Aa receptor (CryR) derived from the silkworm Bombyx mori. We demonstrated that overexpressing CryR in Drosophila melanogaster tissues induced rapid cell death of CryR-expressing cells only, in the presence of Cry1Aa toxin. Cry/CryR system was effective against both proliferating cells in imaginal discs and polyploid postmitotic cells in the fat body. Live imaging analysis of cell ablation revealed swelling and subsequent osmotic lysis of CryR-positive cells after 30 min of incubation with Cry1Aa toxin. Osmotic cell lysis was still triggered when apoptosis, JNK activation, or autophagy was inhibited, suggesting that Cry1Aa-induced necrotic cell death occurred independently of these cellular signaling pathways. Injection of Cry1Aa into the body cavity resulted in specific ablation of CryR-expressing cells, indicating the usefulness of this method for in vivo cell ablation. CONCLUSIONS:With Cry toxins from Bacillus thuringiensis, we developed a novel method for genetic induction of cell necrosis. Our system provides a "proteinous drill" for killing target cells through physical injury of the cell membrane, which can potentially be used to ablate any cell type in any organisms, even those that are resistant to apoptosis or JNK-dependent programmed cell death. |
| 巻・号 | 13 |
| ページ | 48 |
| 公開日 | 2015-7-8 |
| DOI | 10.1186/s12915-015-0160-2 |
| PII | 10.1186/s12915-015-0160-2 |
| PMID | 26152191 |
| PMC | PMC4495774 |
| MeSH | Animals Bacillus thuringiensis / genetics Bacillus thuringiensis Toxins Bacterial Proteins / administration & dosage Bacterial Proteins / genetics* Bacterial Proteins / pharmacology* Bombyx / genetics* Drosophila melanogaster / cytology* Drosophila melanogaster / drug effects Drosophila melanogaster / genetics Endotoxins / administration & dosage Endotoxins / pharmacology* Hemolysin Proteins / administration & dosage Hemolysin Proteins / pharmacology* Insect Proteins MAP Kinase Signaling System Necrosis Optical Imaging Receptors, Cell Surface / genetics* Recombinant Proteins / administration & dosage Recombinant Proteins / pharmacology Up-Regulation* Wings, Animal / cytology* Wings, Animal / drug effects Wings, Animal / metabolism Wings, Animal / pathology* |
| IF | 6.765 |
| 引用数 | 10 |
| WOS 分野 | BIOLOGY |
| リソース情報 | |
| ショウジョウバエ | |