{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T07:55:18Z","timestamp":1787644518727,"version":"build-2736575974"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI166715"],"award-info":[{"award-number":["R01AI166715"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35 GM128786"],"award-info":[{"award-number":["R35 GM128786"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32AI060555"],"award-info":[{"award-number":["T32AI060555"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2025,12,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The intracellular parasite\n                      <jats:italic toggle=\"yes\">Toxoplasma gondii<\/jats:italic>\n                      enhances its dissemination to distant organs by hijacking infected leukocytes via a Trojan Horse mechanism. Upon infecting dendritic cells (DCs),\n                      <jats:italic toggle=\"yes\">Toxoplasma<\/jats:italic>\n                      induces a hypermigratory phenotype characterized by podosome dissolution and formation of F-actin stress fibers. We previously showed that these cytoskeletal changes depend on the effector protein\n                      <jats:italic toggle=\"yes\">Toxoplasma<\/jats:italic>\n                      WAVE complex-interacting protein (\n                      <jats:italic toggle=\"yes\">Tg<\/jats:italic>\n                      WIP) secreted from parasites to infected leukocytes. Here, we identify the host adaptor proteins non-catalytic region of tyrosine kinase adaptor protein 1 and 2 (Nck1\/2) and growth factor receptor-bound protein 2 (Grb2) as direct\n                      <jats:italic toggle=\"yes\">Tg<\/jats:italic>\n                      WIP interactors.\n                      <jats:italic toggle=\"yes\">Tg<\/jats:italic>\n                      WIP mainly uses two distinct proline-rich regions (PRRs) to interact with Nck1 and Grb2. Mutating these PRRs abrogates\n                      <jats:italic toggle=\"yes\">Tg<\/jats:italic>\n                      WIP binding to Nck1 and Grb2 and diminishes podosome dissolution and DC hypermotility. Furthermore, we show that\n                      <jats:italic toggle=\"yes\">Tg<\/jats:italic>\n                      WIP directly interacts with the actin nucleation-promoting factor WAVE regulatory complex (WRC) via a WRC-interacting receptor sequence (WIRS). Disrupting this interaction also influences actin cytoskeletal remodeling and DC hypermotility. Collectively, our data reveal that\n                      <jats:italic toggle=\"yes\">Tg<\/jats:italic>\n                      WIP directly interacts with multiple actin regulators, including Nck1, Grb2, and the WRC, to remodel the actin cytoskeleton of the host cells, elucidating a key mechanism that\n                      <jats:italic toggle=\"yes\">Toxoplasma<\/jats:italic>\n                      exploits to enhance host cell migration and dissemination.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The parasite\n                        <jats:italic toggle=\"yes\">Toxoplasma gondii<\/jats:italic>\n                        spreads throughout the body by hijacking immune cells and boosting their motility. This ability depends on secreted parasite proteins that manipulate the host cell\u2019s actin cytoskeleton. One such effector,\n                        <jats:italic toggle=\"yes\">Toxoplasma gondii<\/jats:italic>\n                        WAVE-interacting protein (\n                        <jats:italic toggle=\"yes\">Tg<\/jats:italic>\n                        WIP), induces dramatic changes in host cell shape and movement, but how it does this has remained unclear. Here, we show that\n                        <jats:italic toggle=\"yes\">Tg<\/jats:italic>\n                        WIP directly interacts with multiple host actin-regulatory proteins using distinct sequence motifs. Disrupting these interactions prevents cytoskeletal remodeling and impairs parasite-induced immune cell migration. Our study reveals that\n                        <jats:italic toggle=\"yes\">Toxoplasma<\/jats:italic>\n                        uses defined motifs to co-opt host signaling hubs that control cell motility. Understanding how pathogens exploit the cytoskeleton not only sheds light on host-pathogen interactions but may also reveal broader principles of cell migration relevant to immunity, cancer, and development.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01874-25","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T13:34:14Z","timestamp":1761917654000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["<i>Toxoplasma<\/i>\n                    effector\n                    <i>Tg<\/i>\n                    WIP hijacks dendritic cell actin and motility via Nck1\/Grb2 and the WAVE complex"],"prefix":"10.1128","volume":"16","author":[{"given":"Pavel","family":"Morales","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05rrcem69","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California","place":["Davis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Kramer","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04rswrd78","id-type":"ROR","asserted-by":"publisher"}],"name":"Roy J. Carver Department of Biochemistry, Biophysics & Molecular Biology, Iowa State University","place":["Ames, USA"]},{"id":[{"id":"https:\/\/ror.org\/05byvp690","id-type":"ROR","asserted-by":"publisher"}],"name":"Departments of Internal Medicine and Biophysics, University of Texas Southwestern Medical Center","place":["Dallas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"de Moraes de Siqueira","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05rrcem69","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California","place":["Davis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbigale J.","family":"Brown","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04rswrd78","id-type":"ROR","asserted-by":"publisher"}],"name":"Roy J. Carver Department of Biochemistry, Biophysics & Molecular Biology, Iowa State University","place":["Ames, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamba Omar","family":"Sangar\u00e9","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05rrcem69","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California","place":["Davis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6366-159X","authenticated-orcid":false,"given":"Baoyu","family":"Chen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04rswrd78","id-type":"ROR","asserted-by":"publisher"}],"name":"Roy J. Carver Department of Biochemistry, Biophysics & Molecular Biology, Iowa State University","place":["Ames, USA"]},{"id":[{"id":"https:\/\/ror.org\/05byvp690","id-type":"ROR","asserted-by":"publisher"}],"name":"Departments of Internal Medicine and Biophysics, University of Texas Southwestern Medical Center","place":["Dallas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0289-7109","authenticated-orcid":true,"given":"Jeroen P. 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