Viral subversion of the cell polarity regulator Scribble

Javorsky, Airah; Humbert, Patrick O.; Kvansakul, Marc

doi:10.1042/bst20221067

Cited by 5 publications

(12 citation statements)

References 103 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our identification of Scrib as a potential partner of the SARS-CoV-2 E protein adds this protein to the large list of viral proteins that interact with this adaptor molecule that facilitates key molecular interactions at distinctive subcellular regions [ 33 ]. Scrib belongs to the LAP (LRR and PDZ) family; it contains 16 Leucine Rich Repeats (LRR), two LAP-specific regions and four PDZ domains.…”

Section: Resultsmentioning

confidence: 99%

Identification of Host PDZ-Based Interactions with the SARS-CoV-2 E Protein in Human Monocytes

Ávila-Flores,

Sánchez-Cabezón,

Ochoa-Echeverría

et al. 2023

IJMS

View full text Add to dashboard Cite

Proteins containing PDZ (post-synaptic density, PSD-95/disc large, Dlg/zonula occludens, ZO-1) domains assemble signaling complexes that orchestrate cell responses. Viral pathogens target host PDZ proteins by coding proteins containing a PDZ-binding motif (PBM). The presence of a PBM in the SARS-CoV-2 E protein contributes to the virus’s pathogenicity. SARS-CoV-2 infects epithelia, but also cells from the innate immune response, including monocytes and alveolar macrophages. This process is critical for alterations of the immune response that are related to the deaths caused by SARS-CoV-2. Identification of E-protein targets in immune cells might offer clues to understanding how SARS-CoV-2 alters the immune response. We analyzed the interactome of the SARS-CoV-2 E protein in human monocytes. The E protein was expressed fused to a GFP tag at the amino terminal in THP-1 monocytes, and associated proteins were identified using a proteomic approach. The E-protein interactome provided 372 partners; only 8 of these harbored PDZ domains, including the cell polarity protein ZO-2, the chemoattractant IL-16, and syntenin. We addressed the expression and localization of the identified PDZ proteins along the differentiation of primary and THP-1 monocytes towards macrophages and dendritic cells. Our data highlight the importance of identifying the functions of PDZ proteins in the maintenance of immune fitness and the viral alteration of inflammatory response.

show abstract

Section: Resultsmentioning

confidence: 99%

Identification of Host PDZ-Based Interactions with the SARS-CoV-2 E Protein in Human Monocytes

Ávila-Flores,

Sánchez-Cabezón,

Ochoa-Echeverría

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…To our knowledge, SseM is unique among Salmonella effectors in containing a functional PBM and as a bacterial protein targeting the DAPC. Several viral oncoproteins target DLG1 to regulate viral virulence [39, 40]. It therefore now essential to investigate the biochemical consequences and physiological significance of SseM’s interaction with DLG1 and DAPC components.…”

Section: Discussionmentioning

confidence: 99%

“…SseM_5 [50] SseM_6_pseudo [40] SseM_7 [24] SseM_8 [20] SseM_9 [18] SseM_10 [14] SseM_11_pseudo [14] SseM_12 [13] SseM_13 [12] SseM_14 [11] SseM_15 [10] SseM_16 [10] SseM_17 [8] SseM_18 [8] SseM_19_pseudo [7] SseM_20 [7] SseM_21_pseudo [7] SseM_22 [7] SseM_23 [7] SseM_24 [6] SseM_25_pseudo [6] SseM_26 [6] SseM_27_pseudo [5] SseM_28 [5] SseM_29 [4] SseM_30 [4] Others [81] Missing [2] SseM variants…”

Section: Figures Andmentioning

confidence: 99%

Modulation ofSalmonellavirulence by a novel SPI-2 injectisome effector that interacts with the dystrophin-associated protein complex

Yu,

Xie,

et al. 2023

Preprint

View full text Add to dashboard Cite

The injectisome encoded bySalmonellapathogenicity island 2 (SPI-2) had been thought to translocate 28 effectors. Here, we used a proteomic approach to characterise the secretome of a clinical strain of invasive non-typhoidalSalmonella entericaserovar Enteritidis, that had been mutated to cause hyper-secretion of the SPI-2 injectisome effectors. Along with many known effectors, we discovered the novel SseM protein.sseMis widely distributed between the five subspecies ofSalmonella enterica,is found in many clinically-relevant serovars, and is co-transcribed withpipB2, aSPI-2 effector gene. Translocation of SseM required a functional SPI-2 injectisome. Following expression in human cells, SseM interacted with five components of the dystrophin-associated protein complex (DAPC), namely β-2-syntrophin, utrophin/ dystrophin, α-catulin, α-dystrobrevin and β-dystrobrevin. The interaction between SseM and β-2-syntrophin and α-dystrobrevin was verified inS.Typhimurium-infected cells and relied on the PDZ domain of β-2-syntrophin and a sequence corresponding to a PDZ-binding motif (PBM) in SseM. A ΔsseMmutant strain had a small competitive advantage over the wild-type strain in theS.Typhimurium/mouse model of systemic disease. This phenotype was complemented by a plasmid expressing wild type SseM fromS.Typhimurium orS.Enteritidis and was dependent on the PBM of SseM. Therefore, a PBM within aSalmonellaeffector mediates interactions with the DAPC and modulates systemic growth of bacteria in mice.ImportanceInSalmonella enterica, the injectisome machinery encoded bySalmonellapathogenicity island 2 (SPI-2) is conserved among the five subspecies and delivers proteins (effectors) into host cells that are required forSalmonellavirulence. The identification and functional characterisation of SPI-2 injectisome effectors advances our understanding of the interplay betweenSalmonellaand its host(s). Using an optimised method for preparing secreted proteins and a clinical isolate of the invasive non-typhoidal (iNTS)Salmonella entericaserovar Enteritidis strain D24359, we identified 22 known SPI-2 injectisome effectors and one new effector - SseM. SseM modulates bacterial growth during murine infection and has a sequence corresponding to a PDZ-binding motif that is essential for interaction with the PDZ-containing host protein β-2-syntrophin and other components of the dystrophin-associated protein complex (DAPC). To our knowledge, SseM is unique amongSalmonellaeffectors in containing a functional PDZ-binding motif and is the first bacterial protein to target the DAPC.

show abstract

“…The N-terminal PTB structural domain of CAPON can bind and function with multiple proteins, such as Scribble, the Synapsin family (including Synapsin I, Synapsin II, and Synapsin III), and Dexras1 [30]. Scribble is a cell polarity protein that is present in the pre-synaptic and post-synaptic membranes [63,64], and it exists as a scaffolding protein. Scribble directly connects with CAPON without the assistance of other proteins.…”

Section: The N-terminal Ptb Structural Domain Of Capon Binds To a Var...mentioning

confidence: 99%

“…Thus, it can be concluded that CAPON is essential for synapse growth in mammals [48]. In addition, Scribble plays a role in cell polarity, differentiation, and migration [37,64,66]. It also functions in tumorigenesis inhibition, and it can bind with Yes-associated protein (YAP) and connect with CAPON to form a triplet complex CAPON-Scribble-YAP [67] (Figure 3).…”

Section: The N-terminal Ptb Structural Domain Of Capon Binds To a Var...mentioning

confidence: 99%

The Physiological Function of nNOS-Associated CAPON Proteins and the Roles of CAPON in Diseases

Xie,

Xing,

et al. 2023

IJMS

View full text Add to dashboard Cite

In this review, the structure, isoform, and physiological role of the carboxy-terminal PDZ ligand of neuronal nitric oxide synthase (CAPON) are summarized. There are three isoforms of CAPON in humans, including long CAPON protein (CAPON-L), short CAPON protein (CAPON-S), and CAPON-S’ protein. CAPON-L includes three functional regions: a C-terminal PDZ-binding motif, carboxypeptidase (CPE)-binding region, and N-terminal phosphotyrosine (PTB) structural domain. Both CAPON-S and CAPON-S’ only contain the C-terminal PDZ-binding motif. The C-terminal PDZ-binding motif of CAPON can bind with neuronal nitric oxide synthase (nNOS) and participates in regulating NO production and neuronal development. An overview is given on the relationship between CAPON and heart diseases, diabetes, psychiatric disorders, and tumors. This review will clarify future research directions on the signal pathways related to CAPON, which will be helpful for studying the regulatory mechanism of CAPON. CAPON may be used as a drug target, which will provide new ideas and solutions for treating human diseases.

show abstract

Viral subversion of the cell polarity regulator Scribble

Cited by 5 publications

References 103 publications

Identification of Host PDZ-Based Interactions with the SARS-CoV-2 E Protein in Human Monocytes

Identification of Host PDZ-Based Interactions with the SARS-CoV-2 E Protein in Human Monocytes

Modulation ofSalmonellavirulence by a novel SPI-2 injectisome effector that interacts with the dystrophin-associated protein complex

The Physiological Function of nNOS-Associated CAPON Proteins and the Roles of CAPON in Diseases

Contact Info

Product

Resources

About