CONICET | Buscador de Institutos y Recursos Humanos

The sumoylated arginine deiminase is critical for Giardia lamblia diferentiation and survival Cecilia Vranych, Gonzalo Mayol, María R. Rivero, María C. Merino, Belkys Maletto, María C. Touz and Andrea S Rópolo. Posttranslational modifications are one of the most effective ways by which evolution has increased the versatility in protein function. Posttranslational conjugation of small ubiquitin-related modifier protein (SUMO) to a specific lysine residue has been shown as one of the major protein modifications that regulate diverse cellular functions, including transcription, nuclear translocation, stress response and chromatin structure. We have studied SUMOylation in the intestinal parasite G. lamblia, and showed that SUMO localize mainly in the cytoplasm of Giardia trophozoites, surrounding the nuclei, and even inside it. By Western blotting, we observed several sumoylated proteins but, at this time, only Arginine Deiminase (ADI) was confirmed as a sumoylated substrate. Recently, it was shown that ADI was involved in the survival and differentiation of the parasite. When ADI was translocated from the cytoplasm to the nuclei during encystation, a reduction cyst wall proteins expression and cyst production was observed. In this work, we demonstrate that the nuclear translocation of ADI depended on sumoylation with this event being crucial for histone citrullination. When the SUMOylation site of ADI was mutated, translocation to the nuclei was avoided and the citrullination of histones impaired. Also, this mutated ADI was unable to behave as the native one thus enhancing cyst production. On the whole, these results suggest that ADI possesses a regulatory role during encystation, with sumoylation and citrullination playing key roles.