SUMO chain formation in Typanosomatids

PAULA A. IRIBARREN; MARIA A. BERAZATEGUI; LUCIA A. DI MARZIO; VANINA E. ALVAREZ

Rio de Janeiro

Simposio; 2nd Advanced School in Genetic Manipulation of Parasitic Protozoa;; 2018

GCRF Global Network for NTDs

SUMOylation is post-translational modification that involves the covalent attachment of the Small Ubiquitin-like Modifier (SUMO) to a wide-range of target proteins. Modification with SUMO is conserved in eukaryotic organisms and plays important regulatory roles in proteins affecting essential cellular processes such as DNA replication and repair, regulation of gene expression and stress response, among others. In T. brucei SUMO is essential for cell cycle progression and in bloodstream parasites (BS), a highly SUMOylated focus located at the active variant surface glycoprotein (VSG) expression site creates a permissive environment for VSG transcription. SUMO can be attached as a single moiety and some SUMO homologs can also be linked to each other via internal lysine residues forming polymeric chains (polySUMOylation). In our lab we were able to show for the first time that TbSUMO is able to form polymers and determined the lysine residues involved in the process.In this work we studied the role of polySUMOylation in BS parasites. By generating transgenic lines unable to form chains and using a mouse model of infection we were able to observe that in absence of polySUMOylation, mice are able to control parasitaemia and successful long term infections are established. Thus although SUMO polymerization is not essential for normal growth, it is involved in important biological processes in the mammalian infectious form of the parasite. Therefore, we analyzed the effects of polySUMOylation on VSG expression and using different approaches we showed that SUMO chains might be involved in regulating differentiation kinetics from the replicative BS form to the fly-preadapted quiescent form. Finally, given that SUMO deconjugating proteases are responsible for the reversible nature of this modification and are ultimately responsible for regulating chain depolymerization dynamics we are currently characterizing these enzymes to understand how this process might be physiologically regulated.