期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2201980119
关键词
endosome; Neuropilin-1; SARS-CoV-2; COVID-19; sorting nexin
资金
- Wellcome Trust [104568/Z/14/Z, 220260/Z/20/Z]
- Medical Research Council (MRC) [MR/L007363/1, MR/P018807/1]
- Lister Institute of Preventive Medicine
- Royal Society Noreen Murray Research Professorship [RSRP/R1/211004]
- Wellcome Trust studentship from the Dynamic Molecular Cell Biology PhD program [203959/Z/16/Z]
- Beca Fundacion Ramon Areces Estudios Postdoctorales en el Extranjero
- BrisSynBio Biotechnology and Biological Sciences Research Council (BBSRC) [BB/L01386X/1]
- National Health and MRC [APP1136021, APP1156493]
- European Research Council under the European Union [856581-CHUbVi]
- UK Research and Innovation/MRC [MR/W005611/1]
- European Regional Development Fund [2014-2020.4.01.15-0012]
- Estonian Research Council [PRG230, EAG79]
- European Research Association (ERA)-NET EuroNanoMed III project iNanogun
- Wellcome Trust [220260/Z/20/Z, 203959/Z/16/Z] Funding Source: Wellcome Trust
Endosomal sorting is important for maintaining cellular homeostasis. The study identified NRP1 as a cargo protein bound and trafficked by the ESCPE-1 complex, which may play a role in intracellular membrane trafficking of NRP1-interacting viruses such as SARS-CoV-2.
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 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 characterized 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 functionalized with the NRP1-interacting peptide of the SARS-CoV-2 spike (S) protein. CRISPR-Cas9 deletion of ESCPE-1 subunits reduces SARS-CoV-2 infection levels in cell culture. ESCPE-1 sorting of NRP1 may therefore play a role in the intracellular membrane trafficking of NRP1-interacting viruses such as SARS-CoV-2.
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