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ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.
Sec. Microbes and Innate Immunity
Volume 14 - 2024 | doi: 10.3389/fcimb.2024.1467440
This article is part of the Research Topic Cell Migration and Tissue Remodeling in Infectious Diseases View all articles

EhVps35, a retromer component, is a key factor in secretion, motility, and tissue invasion by Entamoeba histolytica

Provisionally accepted
Joselin Diaz Joselin Diaz 1Rosario Javier Rosario Javier 1Ausencio Galindo Ausencio Galindo 1Lizbeth Salazar Villatoro Lizbeth Salazar Villatoro 1Sarita Montaño Sarita Montaño 2Esther Orozco Esther Orozco 1*
  • 1 Center for Research and Advanced Studies, National Polytechnic Institute of Mexico (CINVESTAV), México City, Mexico
  • 2 Facultad De Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Culiacán, Sinaloa, Mexico

The final, formatted version of the article will be published soon.

    In humans and Drosophila melanogaster it has been reported the functional convergence of the endosomal sorting complex required for transport (ESCRT) machinery, in charge of selecting ubiquitinated proteins for sorting into multivesicular bodies, and the retromer, the complex responsible for protein recycling to the plasma membrane and Golgi apparatus. Both complexes are codependent for protein sorting recycling, degradation and secretion. In this work, we studied the C isoform of the protein EhVps35 (onwards EhVps35 protein), the central member of the Entamoeba histolytica retromer, and its relation with the ESCRT machinery during virulence events. Our findings revealed that EhVps35 interacts with at least 300 proteins that participate in multiple cellular processes. Laser confocal and transmission electronic microscopy images, as well as secretion assays reveled that EhVps35 is secreted in vesicles together with EhVps23 and EhADH (both ESCRT machinery proteins) and immunoprecipitation, immunofluorescence and assays revealed its relationship with other ESCRT machinery proteins. These interactions were confirmed by molecular docking analysis, that together with results already published evidencing the association between these complexes. The red blood cells stimulus increased EhVps35 secretion. The knockdown of the Ehvps35 gene in trophozoites reduced their capacity to migrate and ability for tissue invasion. This also impacts the cellular localization of ubiquitin, EhVps23 (ESCRT-I) and EhVps32 (ESCRT-III) proteins, strongly suggesting their functional relation. Our results taken together give evidence that EhVps35 is a key factor in E. histolytica virulence mechanisms, and that it together with the ESCRT machinery components and other regulatory proteins, it is involved in vesicle trafficking, secretion, migration, and cell proliferation.

    Keywords: vesicular trafficking, ESCRT machinery, retromer, Entamoeba histolytica, virulence mechanisms, EhVps35

    Received: 19 Jul 2024; Accepted: 30 Aug 2024.

    Copyright: © 2024 Diaz, Javier, Galindo, Salazar Villatoro, Montaño and Orozco. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Esther Orozco, Center for Research and Advanced Studies, National Polytechnic Institute of Mexico (CINVESTAV), México City, Mexico

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