Endogenous pore-forming protein complex targets acidic glycosphingolipids in lipid rafts to initiate endolysosome regulation
Endogenous pore-forming protein complex targets acidic glycosphingolipids in lipid rafts to initiate endolysosome regulation
复制标题
内源性成孔蛋白复合物靶向脂筏中的酸性鞘糖脂以启动内溶酶体调节
DOI：
10.1038/s42003-019-0304-y
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发表时间：
2019-02-11
影响因子：
5.9
通讯作者：
Zhang, Yun
中科院分区：
文献类型：
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作者：
Guo, Xiao-Long;Liu, Ling-Zhen;Zhang, Yun
细菌致孔毒素气溶素样蛋白（ALP）广泛分布于动植物体内。然而，这些ALP的功能研究仍处于起步阶段。β γ-CAT是分泌的成孔蛋白的第一个例子，其功能是通过内吞作用和内溶酶体上的孔形成来调节内溶酶体途径。然而，介导β-γ-CAT作用的特定细胞表面分子仍然难以捉摸。在这里，β-γ-CAT的作用在很大程度上通过添加或消除酸性鞘糖脂（AGSL）而减弱。进一步的研究表明，β γ-CAT的ALP和三叶因子（TFF）亚基分别与神经节苷脂和硫苷脂结合。此外，破坏脂筏在很大程度上损害了β-γ-CAT的行动。最后，β-γ-CAT清除病原体的能力减弱AGSL消除青蛙。这些发现揭示了动物分泌的ALP与TFF复合的先前未知的双重结合模式，其启动ALP诱导的内溶酶体途径调节，最终导致有效的抗菌反应。
Bacterial pore-forming toxin aerolysin-like proteins (ALPs) are widely distributed in animals and plants. However, functional studies on these ALPs remain in their infancy. beta gamma-CAT is the first example of a secreted pore-forming protein that functions to modulate the endolysosome pathway via endocytosis and pore formation on endolysosomes. However, the specific cell surface molecules mediating the action of beta gamma-CAT remain elusive. Here, the actions of beta gamma-CAT were largely attenuated by either addition or elimination of acidic glycosphingolipids (AGSLs). Further study revealed that the ALP and trefoil factor (TFF) subunits of beta gamma-CAT bind to gangliosides and sulfatides, respectively. Additionally, disruption of lipid rafts largely impaired the actions of beta gamma-CAT. Finally, the ability of beta gamma-CAT to clear pathogens was attenuated in AGSL-eliminated frogs. These findings revealed a previously unknown double binding pattern of an animal-secreted ALP in complex with TFF that initiates ALP-induced endolysosomal pathway regulation, ultimately leading to effective antimicrobial responses.