論文 - 詳細
| RRC ID | 34785 |
|---|---|
| 著者 | Jounai N, Kobiyama K, Shiina M, Ogata K, Ishii KJ, Takeshita F. |
| タイトル | NLRP4 negatively regulates autophagic processes through an association with beclin1. |
| ジャーナル | J Immunol |
| Abstract |
Although more than 20 putative members have been assigned to the nucleotide-binding and oligomerization domain-like receptor (NLR) family, their physiological and biological roles, with the exception of the inflammasome, are not fully understood. In this article, we show that NLR members, such as NLRC4, NLRP3, NLRP4, and NLRP10 interact with Beclin1, an important regulator of autophagy, through their neuronal apoptosis inhibitory protein, MHC class II transcription activator, incompatibility locus protein from Podospora anserina, and telomerase-associated protein domain. Among such NLRs, NLRP4 had a strong affinity to the Beclin1 evolutionally conserved domain. Compromising NLRP4 via RNA interference resulted in upregulation of the autophagic process under physiological conditions and upon invasive bacterial infections, leading to enhancement of the autophagic bactericidal process of group A streptococcus. NLRP4 recruited to the subplasma membrane phagosomes containing group A streptococcus and transiently dissociated from Beclin1, suggesting that NLRP4 senses bacterial infection and permits the initiation of Beclin1-mediated autophagic responses. In addition to a role as a negative regulator of the autophagic process, NLRP4 physically associates with the class C vacuolar protein-sorting complex, thereby negatively regulating maturation of the autophagosome and endosome. Collectively, these results provide novel evidence that NLRP4, and possibly other members of the NLR family, plays a crucial role in biogenesis of the autophagosome and its maturation by the association with regulatory molecules, such as Beclin1 and the class C vacuolar protein-sorting complex. |
| 巻・号 | 186(3) |
| ページ | 1646-55 |
| 公開日 | 2011-2-1 |
| DOI | 10.4049/jimmunol.1001654 |
| PII | jimmunol.1001654 |
| PMID | 21209283 |
| MeSH | Adaptor Proteins, Signal Transducing Animals Apoptosis Regulatory Proteins / metabolism Apoptosis Regulatory Proteins / physiology* Autophagy / immunology* Beclin-1 Blood Bactericidal Activity / immunology Cell Line, Tumor Down-Regulation / immunology* Drug Resistance, Bacterial / immunology* HEK293 Cells HeLa Cells Humans Lysosomes / immunology Lysosomes / microbiology Lysosomes / pathology Membrane Proteins / metabolism Membrane Proteins / physiology* Mice Phagosomes / immunology Phagosomes / microbiology Phagosomes / pathology Protein Structure, Tertiary Protein Transport Repressor Proteins / antagonists & inhibitors Repressor Proteins / metabolism Repressor Proteins / physiology* Streptococcal Infections / immunology Streptococcal Infections / metabolism Streptococcal Infections / pathology Streptococcus pyogenes / immunology Vacuoles / immunology Vacuoles / microbiology Vacuoles / pathology |
| IF | 4.886 |
| 引用数 | 102 |
| WOS 分野 | IMMUNOLOGY |
| 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 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 4 |
| 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 | |
| 遺伝子材料 | pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) |