None of both ER GT is essential for viability in C.elegans

BUZZI, L ; BERNINSONE P; PARODI A Y CASTRO O

Mar del Plata Argentina

Congreso; XLIII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular; 2007

Sociedad Argentina de Investigacion Bioquimica y Biologia Molecular

NONE OF BOTH ER GTS IS ESSENTIAL FOR VIABILITY IN C.elegans. 1 Buzzi, L; 2 Berninsone,  P;  1 Parodi,  A; 1 Castro O 1 Fundación Instituto Leloir. Patricias Argentinas 435 Bs As, Argentina 2 University of Nevada, USA  Quality control mechanisms are in place to ensure that newly synthesized   proteins   reach their  properly folded conformation. N-glycans contribute to folding efficiency in the ER by a series of oligosaccharide processing and lectin binding reactions. The UDP-glycoprotein glucosyltransferse (GT) functioning  as a conformational sensor is the key element in this  mechanism.  The two human  GT homologues HUGT1 y HUGT2  share 55 % identity,  but only HUGT1 is active. We undertook a functional characterization of the two putative GTs in the C..elegans  encoded by the F48E3.3  y F26H9.8 genes  . F48E3.3 shows a higher degree of identity (40%) with both human GTs  than  F26H9.8 (35%). We examined the consequences of depleting F26H9.8 and F48E3.3 proteins by RNA interference in wild type animals (WT), in calnexin and calreticulin mutants (cnx-1 y crt-1), in KP948 (RNAi supersensitive strain) and in  SJ4400  containing an ER stress reporter. We found that RNAi against F26H9.8 and F48E3.3 does not cause morphological phenotypes or affect brood size, viability in WT. However, F48E3.3 RNAi elicits expression of the ER stress marker in SJ4400, suggesting the involvement of F483.3 in ER  quality control. RNAi against both GTs in crt-1 and cnx-1 mutants cause some minor pleitropic effects in the larvae and adults, and  RNAi against both protein produce an increase in the lethality of KP948.