An Atypical Class C G-Protein Coupled Receptor (GPCR) Homolog Regulates Movement and Phagocytosis in the Protozoan Parasite 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 a G protein-coupled receptor-like protein, EhGPCR (CL6EHI_096680), predicted to contain a Venus Fly-Trap (VFT) extracellular domain with an Atrial Natriuretic Factor (ANF) receptor domain, as commonly found in the class C GPCR family protein.

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.