sGRP78 enhances selective autophagy of monomeric TLR4 to regulate myeloid cell death.
sGRP78 enhances selective autophagy of monomeric TLR4 to regulate myeloid cell death.
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sGRP78增强单体TLR4的选择性自噬来调节骨髓细胞死亡
DOI：
10.1038/s41419-022-05048-5
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发表时间：
2022-07-07
影响因子：
9
通讯作者：
Lei, Ping
中科院分区：
文献类型：
--
作者：
Wu, Zhenghao;Xu, Zhuoshuo;Zhou, Xiaoqi;Li, Heli;Zhao, Liang;Lv, Yibing;Guo, Yanyan;Shen, Guanxin;He, Yong;Lei, Ping
可溶性葡萄糖调节蛋白 78 (sGRP78) 长期以来一直被认为是炎症消退的介质。我们之前报道过 sGRP78 诱导 TLR4 信号传导缺陷的 TLR4 快速内吞作用。为了阐明其潜在机制，在本研究中，我们研究了 sGRP78 如何影响 TLR4 在骨髓细胞中的行为和运输。研究发现sGRP78通过单体TLR4促进LPS内吞作用。这种内化的单体 TLR4 与 p62-LC3 形成复合物，并在自溶酶体中被降解。此外，sGRP78增强的自噬依赖性TLR4降解导致骨髓细胞凋亡和铁死亡，有助于sGRP78介导的炎症消退。这些报告通过 TLR4 降解建立了内毒素清除和免疫调节的创新机制，通过共享分辨率相关分子模式 (RAMP) — sGRP78 将先天免疫与多种古老过程（包括自噬、细胞凋亡和铁死亡）联系起来。
Soluble glucose regulated protein 78 (sGRP78) has long been suggested as a mediator resolution of inflammation. We previously reported that sGRP78 induced the rapid endocytosis of TLR4 with defective TLR4 signaling. To elucidate the underlying mechanisms, in this study, we investigated how sGRP78 influenced the behavior and trafficking of TLR4 in myeloid cells. It was found that sGRP78 promoted LPS endocytosis with monomeric TLR4. This internalized monomeric TLR4 formed complexes with p62–LC3, and was degraded in autolysosomes. Furthermore, the sGRP78-enhanced autophagy-dependent TLR4 degradation caused apoptosis and ferroptosis in myeloid cells, contributing to the sGRP78-mediated resolution of inflammation. These reports establish innovative mechanisms for endotoxin clearance and immune regulation by TLR4 degradation, linking innate immunity with multiple ancient processes, including autophagy, apoptosis, and ferroptosis, together through a shared resolution-associated molecular pattern (RAMP)—sGRP78.
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影响因子：
13.3
作者：
Giegerich, Annika Klara;Kuchler, Laura;von Knethen, Andreas
通讯作者：
von Knethen, Andreas
影响因子：
21.3
作者：
Cha-Molstad, Hyunjoo;Sung, Ki Sa;Hwang, Joonsung;Kim, Kyoung A.;Yu, Ji Eun;Yoo, Young Dong;Jang, Jun Min;Han, Dong Hoon;Molstad, Michael;Kim, Jung Gi;Lee, Yoon Jee;Zakrzewska, Adriana;Kim, Su-Hyeon;Kim, Sung Tae;Kim, Sun Yong;Lee, Hee Gu;Soung, Nak Kyun;Ahn, Jong Seog;Ciechanover, Aaron;Kim, Bo Yeon;Kwon, Yong Tae
通讯作者：
Kwon, Yong Tae
DOI：
10.1073/pnas.1014156108
发表时间：
2011-01-25
影响因子：
11.1
作者：
Fujita, Ken-ichi;Maeda, Daisuke;Srinivasula, Srinivasa M.
通讯作者：
Srinivasula, Srinivasa M.
影响因子：
21.3
作者：
Gatica D;Lahiri V;Klionsky DJ
通讯作者：
Klionsky DJ
影响因子：
7.3
作者：
Qin K;Ma S;Li H;Wu M;Sun Y;Fu M;Guo Z;Zhu H;Gong F;Lei P;Shen G
通讯作者：
Shen G