Arginine deiminase plays multiple regulatory roles in the biology of Giardia lamblia.

VRANYCH CV; RIVERO MR; TOUZ MC; ROPOLO AS

Mar del Plata, Buenos Aires

Congreso; Reunion Anual de la Sociedad Argentina de Investigacion en Bioquimica y Biologia Molecular.; 2007

Giardia lamblia is a food and waterborne parasite deriving from one of the earliest branches of the eukaryotic lineage. Giardia trophozoites undergo antigenic variation, a process by which the parasite switches its major surface molecules to evade the host’s immune response. These variant-specific surface proteins (VSP) are membrane proteins with a variable N-terminal extracellular region, a well-conserved hydrophobic intramembranous domain, and a perfectly conserved 5 amino acid (CRGKA) C-terminal tail located in the cytoplasm. Although there is extensive data related to the characterization of VSPs, till now it is unclear how the unique structural features of VSP contribute to the biology of Giardia. Here, we demonstrate that arginine deiminase (gADI) binds specifically to the CRGKA cytoplasmic tail of VSPs. We found that the function of ADI in Giardia goes beyond energy production since it is able to deiminate protein-bound arginine and convert it to citrulline, a function restricted to higher eukaryotes. This modification is directly related to the control of the VSP switching in the process of antigenic variation and cell survival. Additionally, during differentiation, gADI seems to play a regulatory role by controlling the expression of encystation specific genes. These results define novel regulatory pathways utilized by Giardia for survival where gADI is a key player.