Rivo Yudhinata Brian Nugraha, Ghulam Jeelani, Herbert J. Santos, Tomoyoshi Nozaki
Amebiasis is a parasitic infection of the human intestines, primarily caused by Entamoeba histolytica. 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, EhVFT (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 EhVFT knockdown reduced parasite motility and phagocytosis of mammalian cell following the reduction of expression of actin cytoskeleton-related genes, including myosin II, villidin, and gelsolin. Our findings suggest that EhVFT plays a role in regulating downstream signaling linked to Entamoeba motility and phagocytosis. This study provides novel insights into an atypical VFT protein in E. histolytica, an area previously understudied. © 2026 Nugraha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Clinical Parasitology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
