Drosophila melanogaster NPC2 proteins bind bacterial cell wall components and may function in immune signal pathways.
Drosophila melanogaster NPC2 proteins bind bacterial cell wall components and may function in immune signal pathways.
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DOI：
10.1016/j.ibmb.2012.04.002
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发表时间：
2012-08
影响因子：
3.8
通讯作者：
Yu, Xiao-Qiang
中科院分区：
文献类型：
--
作者：
Shi, Xiu-Zhen;Zhong, Xue;Yu, Xiao-Qiang
ML(MD-2(髓系分化因子2)相关的脂质识别)是在MD-2、MD-1、NPC2(Niemann-Pick病C2型)和动物、植物和真菌的螨类主要变应原蛋白中发现的一个保守结构域。脊椎动物ML家族中的NPC2和MD-2等蛋白在脂质代谢和免疫信号通路中发挥着重要作用。MD-2是脂多糖(LPS)/Toll样受体4(TLR4)信号通路中必不可少的辅助受体。昆虫含有多个ML基因，可以随意命名为MD-2-或nPC2-like基因。然而，昆虫ML基因是否具有与脊椎动物MD-2类似的功能尚不清楚。在果蝇中，有8个npc2基因(npc2a-h)，根据成熟蛋白中半胱氨酸残基的数量(6、7和8个半胱氨酸)可以进一步将它们分为三个亚组。本研究的目的是探讨果蝇npc2基因是否可能在免疫信号通路中发挥作用。我们选择了代表这三个亚组的npc2a、npc2e和npc2h基因用于本研究。我们发现，重组NPC2a、NPC2e和NPC2h不仅能结合脂多糖和脂蛋白A，还能结合肽聚糖(PG)和脂磷壁酸(LTA)，这一特性在脊椎动物NPC2或MD-2中还没有报道。更重要的是，我们发现在PG刺激的S2细胞中，NPC2a和NPC2e的过表达激活了敌百虫启动子报告，提示NPC2e和NPC2a可能在免疫缺陷(IMD)途径中发挥作用。这是首次关于NPC2蛋白在黑腹毛虫天然免疫中的体外研究。
ML (MD-2 (myeloid differentiation factor 2)-related Lipid-recognition) is a conserved domain identified in MD-2, MD-1, NPC2 (Niemann-Pick disease type C2), and mite major allergen protein from animals, plants, and fungi. Vertebrate members of the ML family proteins, such as NPC2 and MD-2, play important roles in lipid metabolism and immune signaling pathway. MD-2 is an essential co-receptor in the lipopolysaccharide (LPS)/Toll-like receptor 4 (TLR4) signaling pathway. Insects contain multiple ML genes, arbitrarily named md-2- or npc2-like genes. However, whether insect ML genes have functions similar to vertebrate md-2 is unknown. In Drosophila melanogaster, there are eight npc2 genes (npc2a-h), and they can be further divided into three subgroups based on the numbers of cysteine residues (6, 7 and 8 Cys) in the mature proteins. The purpose of this study is to investigate whether any Drosophila npc2 genes may have functions in immune signaling pathways. We chose npc2a, npc2e and npc2h genes representing the three subgroups for this study. We showed that recombinant NPC2a, NPC2e and NPC2h not only bound to LPS and lipid A, but also bound to peptidoglycan (PG) and lipoteichoic acid (LTA), a property that has not been reported previously for vertebrate NPC2 or MD-2. More importantly, we showed that over-expression of NPC2a and NPC2e activated diptericin promoter reporter in S2 cells stimulated by PG, suggesting that NPC2e and NPC2a may play a role in the immune deficiency (Imd) pathway. This is the first in vitro study about NPC2 proteins in innate immunity of D. melanogaster.
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影响因子：
6.7
作者：
Dong Y;Aguilar R;Xi Z;Warr E;Mongin E;Dimopoulos G
通讯作者：
Dimopoulos G
影响因子：
--
作者：
Ganesan, Sandhya;Aggarwal, Kamna;Paquette, Nicholas;Silverman, Neal
通讯作者：
Silverman, Neal
影响因子：
4.8
作者：
Ishii, Kenichi;Hamamoto, Hiroshi;Sekimizu, Kazuhisa
通讯作者：
Sekimizu, Kazuhisa
DOI：
10.1073/pnas.92.21.9465
发表时间：
1995-10-10
影响因子：
11.1
作者：
LEMAITRE, B;KROMERMETZGER, E;HOFFMANN, JA
通讯作者：
HOFFMANN, JA
影响因子：
3.6
作者：
Ao, Jing-qun;Ling, Erjun;Yu, Xiao-Qiang
通讯作者：
Yu, Xiao-Qiang