{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T06:46:57Z","timestamp":1747205217682,"version":"3.40.5"},"posted":{"date-parts":[[2024,6,26]]},"group-title":"In Review","reference-count":0,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T00:00:00Z","timestamp":1719360000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,6,6]]},"abstract":"<title>Abstract<\/title>\n        <p>The obligate intracellular parasite <italic>Toxoplasma gondii<\/italic> causes life-threatening toxoplasmosis to immunocompromised individuals. The pathogenesis of <italic>Toxoplasma<\/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 <italic>Tg<\/italic>WIP, a protein secreted from <italic>Toxoplasma<\/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 <italic>Tg<\/italic>WIP harbors two SH2-binding motifs that interact with tyrosine phosphatases Shp1 and Shp2, leading to phosphatase activation. DCs infected with <italic>Toxoplasma<\/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 <italic>Toxoplasma<\/italic> expressing a mutant <italic>Tg<\/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 <italic>Tg<\/italic>WIP-Shp1\/2 dependent manner. Collectively, the data uncover a molecular mechanism by which <italic>Tg<\/italic>WIP modulates the migration dynamics of infected DCs <italic>in vitro<\/italic>.<\/p>","DOI":"10.21203\/rs.3.rs-4539584\/v1","type":"posted-content","created":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T15:19:17Z","timestamp":1719415157000},"source":"Crossref","is-referenced-by-count":0,"title":["The Toxoplasma secreted effector TgWIP modulates dendritic cell motility by activating host tyrosine phosphatases Shp1 and Shp2"],"prefix":"10.21203","author":[{"given":"Pavel","family":"Morales","sequence":"first","affiliation":[{"name":"University of California Davis"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abbigale J.","family":"Brown","sequence":"additional","affiliation":[{"name":"Iowa State University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lamba Omar","family":"Sangare","sequence":"additional","affiliation":[{"name":"University of California Davis"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Iowa State University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Kuihon","sequence":"additional","affiliation":[{"name":"Iowa State University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baoyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Iowa State University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0289-7109","authenticated-orcid":false,"given":"Jeroen","family":"Saeij","sequence":"additional","affiliation":[{"name":"University of California Davis School of Veterinary Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/www.researchsquare.com\/article\/rs-4539584\/v1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.researchsquare.com\/article\/rs-4539584\/v1.html","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T15:19:22Z","timestamp":1719415162000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.researchsquare.com\/article\/rs-4539584\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,26]]},"references-count":0,"URL":"https:\/\/doi.org\/10.21203\/rs.3.rs-4539584\/v1","relation":{},"subject":[],"published":{"date-parts":[[2024,6,26]]},"subtype":"preprint"}}