Arginine deiminase has multiple regulatory roles in the biology of Giardia lamblia.
The protozoan parasite Giardia lamblia uses arginine deiminase (ADI) to produce energy from free L-arginine under anaerobic conditions. In this work, we demonstrate that, in addition to its known role as a metabolic enzyme, it also functions as a peptidylarginine deiminase, converting protein-bound arginine into citrulline. G. lamblia ADI specifically binds to and citrullinates the arginine in the conserved CRGKA tail of variant-specific surface proteins (VSPs), affecting both antigenic switching and antibody-mediated cell death. During encystation, ADI translocates from the cytoplasm to the nuclei and appears to play a regulatory role in the expression of encystation-specific genes. ADI is also sumoylated, which might modulate its activity. Our findings reveal a dual role played by ADI and define novel regulatory pathways used by Giardia for survival.
Touz
Maria Carolina
MC
Instituto de Investigación Medica Mercedes y Martín Ferreyra, INIMEC - CONICET, Friuli 2434, Cordoba, Argentina. ctouz@immf.uncor.edu
Rópolo
Andrea Silvana
AS
Rivero
Maria Romina
MR
Vranych
Cecilia Veronica
CV
Conrad
John Thomas
JT
Svard
Staffan Gunnar
SG
Nash
Theodore Elliott
TE
D000818:Animals; D000940:Antigenic Variation; D000953:Antigens, Protozoan / Q000378:metabolism; D016923:Cell Death; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000201:enzymology; D002956:Citrulline / Q000378:metabolism; D016829:Giardia lamblia / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development; D006867:Hydrolases / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D000076342:Protein-Arginine Deiminases; D015800:Protozoan Proteins / Q000378:metabolism
D000953:Antigens, Protozoan; D015800:Protozoan Proteins; C072464:variant surface protein H7, Giardia lamblia; D002956:Citrulline; D006867:Hydrolases; D000076342:Protein-Arginine Deiminases