NLRP4 negatively regulates autophagic processes through an association with beclin1.

点击翻译按钮获取中文摘要

In this study, we show that NLRP4 interact with Beclin1, an important regulator of autophagy, through their NACHT domain. Among such NLRs, NLRP4 had a strong affinity to the Beclinl evolutionally conserved domain. Conlpromising NLRP4 via RNA interference resulted in an upregulation of the autophagic process under physiological conditions and upon invasive bacterial infections, leading to enhancement of the autophagic bactericidal process against group A streptococcus (GAS). NLRP4 recruited to the sub-plasma membrane phagosomes containing GAS and transiently dissociated from Beclin1, suggesting that NLRP4 senses bacterial infection and permits the initiation of Beclin1-mediated autophagic responses. In addition to such a role as a negative regulator of the autophagic process, NLRP4 physically associates with the class C vacuolar protein sorting (C-VPS) complex, thereby negatively regulates the maturation of the autophagosome and endosome. Collectively, these results provide novel evidence that NLRP4, and possibly some other members of the NLR family, play a crucial role in biogenesis of the autophagosome and its maturation by the association with the regulatory molecules such as Beclinl and the C-VPS complex.