The Toxoplasma secreted effector TgWIP modulates dendritic cell motility by activating host tyrosine phosphatases Shp1 and Shp2

• DOI: 10.1007/s00018-024-05283-3
• Publication Date: 2024-07-09T02:01:41Z
• Authors: Pavel Morales; Abbigale J. Brown; Lamba Omar Sangaré; Sheng Yang; Simon V.N.P. Kuihon; Baoyu Chen; Jeroen P.J. Saeij
• Keywords: Filopodia; Pseudopodia; Intracellular parasite

The obligate intracellular parasite Toxoplasma gondii causes life-threatening toxoplasmosis to immunocompromised individuals. pathogenesis of relies on its swift dissemination the central nervous system through a 'Trojan Horse' mechanism using infected leukocytes as carriers. Previous work found TgWIP, protein secreted from Toxoplasma, played role in altering actin cytoskeleton and promoting cell migration dendritic cells (DCs). However, behind these changes was unknown. Here, we report that TgWIP harbors two SH2-binding motifs interact with tyrosine phosphatases Shp1 Shp2, leading phosphatase activation. DCs exhibited hypermigration, accompanying enhanced F-actin stress fibers increased membrane protrusions such filopodia pseudopodia. By contrast, phenotypes were abrogated expressing mutant lacking motifs. We further demonstrated Rho-associated kinase (Rock) is involved induction phenotypes, TgWIP-Shp1/2 dependent manner. Collectively, data uncover molecular by which modulates dynamics vitro.