Anterograde trafficking of Toll-like receptors requires the cargo sorting adaptors TMED-2 and 7.

IF 3.6 3区生物学 Q3 CELL BIOLOGY

Traffic Pub Date : 2023-11-01 Epub Date: 2023-07-26 DOI:10.1111/tra.12912

Julia E J Holm, Sandro G Soares, Martyn F Symmons, Afiqah Saleh Huddin, Martin C Moncrieffe, Nicholas J Gay

引用次数: 0

Abstract

Toll-Like Receptors (TLRs) play a pivotal role in immunity by recognising conserved structural features of pathogens and initiating the innate immune response. TLR signalling is subject to complex regulation that remains poorly understood. Here we show that two small type I transmembrane receptors, TMED2 and 7, that function as cargo sorting adaptors in the early secretory pathway are required for transport of TLRs from the ER to Golgi. Protein interaction studies reveal that TMED7 interacts with TLR2, TLR4 and TLR5 but not with TLR3 and TLR9. On the other hand, TMED2 interacts with TLR2, TLR4 and TLR3. Dominant negative forms of TMED7 suppress the export of cell surface TLRs from the ER to the Golgi. By contrast TMED2 is required for the ER-export of both plasma membrane and endosomal TLRs. Together, these findings suggest that association of TMED2 and TMED7 with TLRs facilitates anterograde transport from the ER to the Golgi.

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Toll样受体的反向贩运需要货物分拣适配器TMED-2和7。

Toll样受体（TLRs）通过识别病原体的保守结构特征和启动先天免疫反应，在免疫中发挥着关键作用。TLR信号传导受到复杂的调控，但人们对此知之甚少。在这里，我们发现两种小的I型跨膜受体，TMED2和7，在早期分泌途径中作为货物分拣适配器发挥作用，是将TLR从内质网转运到高尔基体所必需的。蛋白质相互作用研究表明，TMED7与TLR2、TLR4和TLR5相互作用，但与TLR3和TLR9不相互作用。另一方面，TMED2与TLR2、TLR4和TLR3相互作用。TMED7的显性阴性形式抑制细胞表面TLR从内质网向高尔基体的输出。相比之下，TMED2是质膜和内体TLR的ER输出所必需的。总之，这些发现表明TMED2和TMED7与TLRs的结合促进了从ER到高尔基体的顺行运输。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Traffic 生物-细胞生物学

CiteScore

8.10

自引率

2.20%

发文量

审稿时长

2 months

期刊介绍： Traffic encourages and facilitates the publication of papers in any field relating to intracellular transport in health and disease. Traffic papers span disciplines such as developmental biology, neuroscience, innate and adaptive immunity, epithelial cell biology, intracellular pathogens and host-pathogen interactions, among others using any eukaryotic model system. Areas of particular interest include protein, nucleic acid and lipid traffic, molecular motors, intracellular pathogens, intracellular proteolysis, nuclear import and export, cytokinesis and the cell cycle, the interface between signaling and trafficking or localization, protein translocation, the cell biology of adaptive an innate immunity, organelle biogenesis, metabolism, cell polarity and organization, and organelle movement. All aspects of the structural, molecular biology, biochemistry, genetics, morphology, intracellular signaling and relationship to hereditary or infectious diseases will be covered. Manuscripts must provide a clear conceptual or mechanistic advance. The editors will reject papers that require major changes, including addition of significant experimental data or other significant revision. Traffic will consider manuscripts of any length, but encourages authors to limit their papers to 16 typeset pages or less.

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