SARS‐CoV‐2 spike protein harnesses SNX27‐mediated endocytic recycling pathway

Zhao, Lin; Zhong, Kunhong; Zhao, Jia; Xin, Yong; Tong, Aiping; Jia, Da

doi:10.1002/mco2.92

Cited by 13 publications

(20 citation statements)

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“…Consistent with our study, recent studies found that ACE2 surface localization was mediated by SNX27 and SARS-CoV-2 S associated with SNX27 ( 5 , 6 , 7 , 8 ). However, those studies did not explore the role for SARS-CoV-2 S in the endocytic recycling of ACE2.…”

Section: Dear Editorsupporting

confidence: 93%

Inhibition of endocytic recycling of ACE2 by SARS-CoV-2 S protein partially explains multiple COVID-19 related diseases caused by ACE2 reduction

Ren¹,

Lv²,

Zhang³

2022

Journal of Infection

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Section: Dear Editorsupporting

confidence: 93%

Inhibition of endocytic recycling of ACE2 by SARS-CoV-2 S protein partially explains multiple COVID-19 related diseases caused by ACE2 reduction

Ren¹,

Lv²,

Zhang³

2022

Journal of Infection

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“…Interestingly, additional pathogens hijack ESCPE-1 cargo recognition to promote intracellular survival 2,3,44 , and SNX5 has also recently been identified as a key regulator of innate cellular immunity against a range of viruses 45 . Genome wide CRISPR screens and biochemical studies have identified multiple endosomal sorting machineries that facilitate SARS-CoV-2 infection, including components of the retromer, retriever and COMMD/CCDC22/CCDC93 (CCC) complexes [46][47][48][49][50][51] . Here, we suggest that ESCPE-1 sequence-dependent cargo sorting also plays a role in regulating the endosomal dynamics exploited during SARS-CoV-2 infection, potentially expanding the scope of pathogens that exploit can this complex.…”

Section: Discussionmentioning

confidence: 99%

ESCPE-1 Mediates Retrograde Endosomal Sorting of the SARS-CoV-2 Host Factor Neuropilin-1

Simonetti

Daly

Simón‐Gracia

et al. 2022

Preprint

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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.

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“…Interestingly, SNX27 was recently reported to interact with the SARS-CoV-2 spike (S) protein through its PDZ domain to facilitate S protein surface expression, although the viral protein does not contain a PBM. SARS-CoV-2 may facilitate virion trafficking to establish virus infection by this strategy [42]. Overall, among the ACE2 binders, some are known to interact with viruses such as SNX27 [43,44], MAST2, PTPN3 and SCRIB [45].…”

Section: Discussionmentioning

confidence: 99%

PDZ-Containing Proteins Targeted by the ACE2 Receptor

Caillet‐Saguy

Wolff

2021

Viruses

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Angiotensin-converting enzyme 2 (ACE2) is a main receptor for SARS-CoV-2 entry to the host cell. Indeed, the first step in viral entry is the binding of the viral trimeric spike (S) protein to ACE2. Abundantly present in human epithelial cells of many organs, ACE2 is also expressed in the human brain. ACE2 is a type I membrane protein with an extracellular N-terminal peptidase domain and a C-terminal collectrin-like domain that ends with a single transmembrane helix and an intracellular 44-residue segment. This C-terminal segment contains a PDZ-binding motif (PBM) targeting protein-interacting domains called PSD-95/Dlg/ZO-1 (PDZ). Here, we identified the human PDZ specificity profile of the ACE2 PBM using the high-throughput holdup assay and measuring the binding intensities of the PBM of ACE2 against the full human PDZome. We discovered 14 human PDZ binders of ACE2 showing significant binding with dissociation constants’ values ranging from 3 to 81 μM. NHERF, SHANK, and SNX27 proteins found in this study are involved in protein trafficking. The PDZ/PBM interactions with ACE2 could play a role in ACE2 internalization and recycling that could be of benefit for the virus entry. Interestingly, most of the ACE2 partners we identified are expressed in neuronal cells, such as SHANK and MAST families, and modifications of the interactions between ACE2 and these neuronal proteins may be involved in the neurological symptoms of COVID-19.

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SARS‐CoV‐2 spike protein harnesses SNX27‐mediated endocytic recycling pathway

Cited by 13 publications

References 50 publications

Inhibition of endocytic recycling of ACE2 by SARS-CoV-2 S protein partially explains multiple COVID-19 related diseases caused by ACE2 reduction

Inhibition of endocytic recycling of ACE2 by SARS-CoV-2 S protein partially explains multiple COVID-19 related diseases caused by ACE2 reduction

ESCPE-1 Mediates Retrograde Endosomal Sorting of the SARS-CoV-2 Host Factor Neuropilin-1

PDZ-Containing Proteins Targeted by the ACE2 Receptor

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