Department of Medicine, University of Cambridge, The West Forvie Building, Robinson Way, Cambridge, CB2 0SZ, UK.
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui-Jin Hospital affiliated to Shanghai JiaoTong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China.
Nat Commun. 2017 Jun 28;8:15986. doi: 10.1038/ncomms15986.
Excessive activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome is involved in many chronic inflammatory diseases, including cardiovascular and Alzheimer's disease. Here we show that microtubule-affinity regulating kinase 4 (MARK4) binds to NLRP3 and drives it to the microtubule-organizing centre, enabling the formation of one large inflammasome speck complex within a single cell. MARK4 knockdown or knockout, or disruption of MARK4-NLRP3 interaction, impairs NLRP3 spatial arrangement and limits inflammasome activation. Our results demonstrate how an evolutionarily conserved protein involved in the regulation of microtubule dynamics orchestrates NLRP3 inflammasome activation by controlling its transport to optimal activation sites, and identify a targetable function for MARK4 in the control of innate immunity.
NLR 家族富含pyrin 域蛋白 3（NLRP3）炎性小体的过度激活与许多慢性炎症性疾病有关，包括心血管疾病和阿尔茨海默病。在这里，我们表明微管亲和调节激酶 4（MARK4）与 NLRP3 结合，并将其驱动到微管组织中心，使单个细胞内形成一个大型炎性小体斑点复合物。MARK4 敲低或敲除，或破坏 MARK4-NLRP3 相互作用，会损害 NLRP3 的空间排列并限制炎性小体的激活。我们的研究结果表明，参与微管动力学调节的进化保守蛋白如何通过控制其向最佳激活部位的运输来调节 NLRP3 炎性小体的激活，并确定 MARK4 在控制先天免疫中的靶向功能。
Zotero 插件
