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Mol. Life Sci."],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The obligate intracellular parasite <jats:italic>Toxoplasma gondii<\/jats:italic> causes life-threatening toxoplasmosis to immunocompromised individuals. The pathogenesis of <jats:italic>Toxoplasma<\/jats:italic> relies on its swift dissemination to the central nervous system through a \u2018Trojan Horse\u2019 mechanism using infected leukocytes as carriers. Previous work found <jats:italic>Tg<\/jats:italic>WIP, a protein secreted from <jats:italic>Toxoplasma<\/jats:italic>, played a role in altering the actin cytoskeleton and promoting cell migration in infected dendritic cells (DCs). However, the mechanism behind these changes was unknown. Here, we report that <jats:italic>Tg<\/jats:italic>WIP harbors two SH2-binding motifs that interact with tyrosine phosphatases Shp1 and Shp2, leading to phosphatase activation. DCs infected with <jats:italic>Toxoplasma<\/jats:italic> exhibited hypermigration, accompanying enhanced F-actin stress fibers and increased membrane protrusions such as filopodia and pseudopodia. By contrast, these phenotypes were abrogated in DCs infected with <jats:italic>Toxoplasma<\/jats:italic> expressing a mutant <jats:italic>Tg<\/jats:italic>WIP lacking the SH2-binding motifs. We further demonstrated that the Rho-associated kinase (Rock) is involved in the induction of these phenotypes, in a <jats:italic>Tg<\/jats:italic>WIP-Shp1\/2 dependent manner. Collectively, the data uncover a molecular mechanism by which <jats:italic>Tg<\/jats:italic>WIP modulates the migration dynamics of infected DCs in vitro.<\/jats:p>","DOI":"10.1007\/s00018-024-05283-3","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T02:01:41Z","timestamp":1720490501000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Toxoplasma secreted effector TgWIP modulates dendritic cell motility by activating host tyrosine phosphatases Shp1 and Shp2"],"prefix":"10.1007","volume":"81","author":[{"given":"Pavel","family":"Morales","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbigale J.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamba Omar","family":"Sangar\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon V.N.P.","family":"Kuihon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoyu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0289-7109","authenticated-orcid":false,"given":"Jeroen P.J.","family":"Saeij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,9]]},"reference":[{"key":"5283_CR1","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1016\/j.ijpara.2009.04.003","volume":"39","author":"G Pappas","year":"2009","unstructured":"Pappas G, Roussos N, Falagas ME (2009) Toxoplasmosis snapshots: global status of Toxoplasma Gondii seroprevalence and implications for pregnancy and congenital toxoplasmosis. 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