THE Ca e n o h a r b d i t is e l e g a n s UDP-GLUCOSE: GLY C OP R OTEI N GL U C OS Y LT R A N S FE R A SE HOMOLOGUES HAVE NOT IDENTICAL FUNCTIONS

BUZZI, L; SIMONETTA SH; ARMANDO J. PARODI .; CASTRO OA.

Potrero de los Funes

Congreso; XLVII reunión Anual de la Sociedad Argentina de Bioquímica y Biología Molecular; 2011

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

THE Ca e n o h a r b d i t is e l e g a n s UDP-GLUCOSE: GLY C OP R OTEI N GL U C OS Y LT R A N S FE R A SEHOMOLOGUES HAVE NOT IDENTICAL FUNCTIONS Buzzi LI , Simonetta SH , Parodi AJ , Castro O . Fundación Instituto Leloir, IIBBA-CONICET. Universidad de Buenos Aires, Bs. Aires, Argentina.E-mail: lbuzzi@leloir.org.ar The UDP-Glc:glycoprotein glucosyltransferase (UGGT) is the key component of the glycoprotein folding quality control mechanism in the endoplasmic reticulum (ER). It behaves as a sensor of glycoprotein conformation as it exclusively glucosylatesglycoproteins not displaying their native conformations. Mostspecies have only one gene coding for UGGT-like proteins whileEuteleostomi, Caenorhabditis and humans have two homologues. In humans HUGT1 but not HUGT2 displayed UGGT activity andwas upregulated under ER stress conditions. Bioinformaticsanalysis showed that in C.elegans there are two open readingframes F48E3.3 (uggt-1) and F26H9.8 (uggt-2) coding for UGGT homologues. Here we report that C.elegans expresses an activeUGGT protein localized in the ER encoded by the uggt-1 gene. Weconstructed transgenic worms carrying the Puggt-1::gfp constructand found that UGGT-1 is expressed in cells of the nervous systemand is upregulated under ER stress. Real time PCR analysis showedthat both uggt-1 and uggt-2 are expressed during the entire C. elegans life cycle but at very different levels, being uggt-2expression at most 3% of uggt-1. Depletion of UGGT-1 by RNAiresulted in a reduced lifespan and that of UGGT-1 and UGGT-2 in adelay in development. With an ER stressor drug the delay wasincreased. We conclude that UGGT-1 and UGGT-2 play a protective role under ER stress.