The COP II adaptor protein TMED7 is required to initiate and mediate the delivery of TLR4 to the plasma membrane.
The COP II adaptor protein TMED7 is required to initiate and mediate the delivery of TLR4 to the plasma membrane.
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DOI：
10.1126/scisignal.2005275
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发表时间：
2014-07-29
影响因子：
7.3
通讯作者：
Gay NJ
中科院分区：
文献类型：
--
作者：
Liaunardy-Jopeace A;Bryant CE;Gay NJ
Toll-like receptor 4 (TLR4), the receptor for the bacterial product endotoxin, is subject to multiple points of regulation at the levels of signaling, biogenesis, and trafficking. Dysregulation of TLR4 signaling can cause serious inflammatory diseases, such as sepsis. We found that the p24 family protein TMED7 (transmembrane emp24 protein transport domain containing 7) is required for the trafficking of TLR4 from the endoplasmic reticulum to the cell surface through the Golgi. TMED7 formed a stable complex with the ectodomain of TLR4, an interaction that required the coiled-coil and GOLD domains, but not the cytosolic, COP II sorting motif, of TMED7. Depletion of TMED7 reduced TLR4 signaling mediated by the adaptor protein MyD88, but not that mediated by the adaptor proteins TRAM and TRIF. Truncated forms of TMED7 lacking the COP II sorting motif or the transmembrane domain were mislocalized and resulted in constitutive activation of TLR4 signaling. Together, these results support the hypothesis that p24 proteins perform a quality control step by recognizing correctly folded anterograde cargo, such as TLR4, in early secretory compartments and facilitating the translocation of this cargo to the cell surface.
