The Essential Role of Sorting Nexin 5 in Virus-Induced Autophagy

Li, Dong-Yi; Wen, Jun-Hao; Liang, Shan; Tang, Ji‐Xin

doi:10.3389/fimmu.2022.947384

Cited by 1 publication

(1 citation statement)

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“…An intricate competition exists between pathogens and their hosts [24][25][26] in controlling cellular trafficking regulated by SNXs. Several intracellular pathogens hijack SNXs as a part of the mechanisms used to support their intracellular survival without themselves expressing SNXs.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the First Secreted Sorting Nexin Identified in the Leishmania Protists

Tziouvara,

Petsana,

Kourounis

et al. 2024

IJMS

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Proteins of the sorting nexin (SNX) family present a modular structural architecture with a phox homology (PX) phosphoinositide (PI)-binding domain and additional PX structural domains, conferring to them a wide variety of vital eukaryotic cell’s functions, from signal transduction to membrane deformation and cargo binding. Although SNXs are well studied in human and yeasts, they are poorly investigated in protists. Herein, is presented the characterization of the first SNX identified in Leishmania protozoan parasites encoded by the LdBPK_352470 gene. In silico secondary and tertiary structure prediction revealed a PX domain on the N-terminal half and a Bin/amphiphysin/Rvs (BAR) domain on the C-terminal half of this protein, with these features classifying it in the SNX-BAR subfamily of SNXs. We named the LdBPK_352470.1 gene product LdSNXi, as it is the first SNX identified in Leishmania (L.) donovani. Its expression was confirmed in L. donovani promastigotes under different cell cycle phases, and it was shown to be secreted in the extracellular medium. Using an in vitro lipid binding assay, it was demonstrated that recombinant (r) LdSNXi (rGST-LdSNXi) tagged with glutathione-S-transferase (GST) binds to the PtdIns3P and PtdIns4P PIs. Using a specific a-LdSNXi antibody and immunofluorescence confocal microscopy, the intracellular localization of endogenous LdSNXi was analyzed in L. donovani promastigotes and axenic amastigotes. Additionally, rLdSNXi tagged with enhanced green fluorescent protein (rLdSNXi-EGFP) was heterologously expressed in transfected HeLa cells and its localization was examined. All observed localizations suggest functions compatible with the postulated SNX identity of LdSNXi. Sequence, structure, and evolutionary analysis revealed high homology between LdSNXi and the human SNX2, while the investigation of protein–protein interactions based on STRING (v.11.5) predicted putative molecular partners of LdSNXi in Leishmania.

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Section: Introductionmentioning

confidence: 99%