CONICET | Buscador de Institutos y Recursos Humanos

Giardia lamblia differentiation from the trophozoite to the cyst stage is critical for the parasite survival in the environment and for disease transmission. Despite recent discoveries in the field of Giardia encystations, our understanding of the molecular mechanisms initiating and regulating gene expression during this critical process remains incomplete. In a previous work, we analyzed the role of SUMO protein and the putative enzymes of the SUMOylation pathway in Giardia. At present, only the enzyme Arginine Deiminase (ADI) was confirmed as a SUMOylated substrate. ADI is involved in the survival of the parasite and catalyzes the modification of arginine residues to citrulline in the cytoplasmic tail of surface proteins. During encystation, however, ADI translocates from the cytoplasm to the nuclei. In this work, by site-specific mutation of the ADI SUMOylation site, we observed that these transgenic cells failed to enter the nucleus at the first steps of encystation but shuttled in the nuclei late during this process through classical nuclear localization signals. Inside the nuclei, ADI modifies histones by citrullination, and this modification is probably involved in the downregulation of CWP expression and cyst wall formation. Our results strongly indicate that ADI plays a regulatory role during encystation in which posttranslational modifications of proteins are key players.