ESCPE-1 mediates retrograde endosomal sorting of the SARS-CoV-2 host factor Neuropilin-1-猫眼课题宝

DOI：

10.1101/2022.01.20.477115

发表时间：

2022-01

期刊：

Proceedings of the National Academy of Sciences of the United States of America

影响因子：

11.1

通讯作者：

中科院分区：

综合性期刊1区

文献类型：

作者：

Boris Simonetti;James L. Daly;L. Simón‐Gracia;Katja Klein;S. Weeratunga;Carlos Antón-Plágaro;Allan Tobi;L. Hodgson;Phillip A. Lewis;K. Heesom;D. Shoemark;A. Davidson;B. Collins;T. Teesalu;Y. Yamauchi;P. Cullen

内体分选通过将跨膜蛋白和相关蛋白质和脂质（称为“货物”）从内体网络再循环到多个亚细胞目的地（包括逆行运输到trans-Golgi网络（TGN））来维持细胞内稳态。病毒和细菌病原体破坏逆行运输机制，以促进传染性。在这里，我们开发了一个蛋白质组学筛选，以确定新的逆行货物蛋白的内体SNX-BAR分选复合物促进出口-1（ESCPE-1）。使用这种方法，我们确定神经纤毛蛋白-1（NRP 1），一个最近表征的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的宿主因子，作为货物直接绑定和运输的ESCPE-1。ESCPE-1介导与SARS-CoV-2刺突蛋白的NRP 1相互作用肽功能化的工程纳米颗粒的逆行运输。因此，NRP 1的ESCPE-1分选可能在NRP 1相互作用病毒（如SARS-CoV-2）的细胞内膜运输中发挥作用。

Endosomal sorting maintains cellular homeostasis by recycling transmembrane proteins and associated proteins and lipids (termed ‘cargoes’) from the endosomal network to multiple subcellular destinations, including retrograde traffic to the trans-Golgi network (TGN). Viral and bacterial pathogens subvert retrograde trafficking machinery to facilitate infectivity. Here, we develop a proteomic screen to identify novel retrograde cargo proteins of the Endosomal SNX-BAR Sorting Complex Promoting Exit-1 (ESCPE-1). Using this methodology, we identify Neuropilin-1 (NRP1), a recently characterised host factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as a cargo directly bound and trafficked by ESCPE-1. ESCPE-1 mediates retrograde trafficking of engineered nanoparticles functionalised with the NRP1-interacting peptide of the SARS-CoV-2 Spike protein. ESCPE-1 sorting of NRP1 may therefore play a role in the intracellular membrane trafficking of NRP1-interacting viruses such as SARS-CoV-2.

ESCPE-1 mediates retrograde endosomal sorting of the SARS-CoV-2 host factor Neuropilin-1

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