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Its pathogenesis relies on the environmental sensing-induced cytoskeletal remodeling as the basic mechanism for motility and tissue invasion. We identified and characterized an atypical Venus Fly-Trap (VFT) receptor protein,\n                    <jats:italic>Eh<\/jats:italic>\n                    VFT (CL6EHI_096680). While it shares homology with the ligand-binding domain of class C GPCRs, it is phylogenetically related to the Periplasmic Binding Protein (PBP) superfamily. This protein is uniquely lacking a transmembrane domain. Instead, the glycosylphosphatidylinositol (GPI) anchor is responsible for its cell membrane localization. Removal of the GPI signal led to unexpected mitosomal localization, highlighting the importance of GPI modification in subcellular targeting. Functional studies revealed that\n                    <jats:italic>Eh<\/jats:italic>\n                    VFT knockdown reduced parasite motility and phagocytosis of mammalian cells following the reduction of expression of actin cytoskeleton-related genes, including myosin II, villidin, and gelsolin. Our findings suggest that\n                    <jats:italic>Eh<\/jats:italic>\n                    VFT plays a role in regulating downstream signaling linked to\n                    <jats:italic>Entamoeba<\/jats:italic>\n                    motility and phagocytosis. This study provides novel insights into an atypical VFT protein in\n                    <jats:italic>E. histolytica<\/jats:italic>\n                    , an area previously understudied.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014019","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T18:39:13Z","timestamp":1772217553000},"page":"e1014019","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["An atypical venus fly trap domain receptor regulates motility and phagocytosis in the protozoan parasite Entamoeba histolytica"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4314-6961","authenticated-orcid":true,"given":"Rivo Yudhinata 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