[
European Worm Meeting,
2006]
Proteins are vitally important macromolecules that perform diverse roles in all organisms. A common feature of any protein is its requirement for a specific three-dimensional structure for biological function. In many secreted and membrane-associated proteins this three-dimensional structure is stabilised by intra- or intermolecular disulphide bonds, which are usually formed post-translationally in the endoplasmic reticulum (ER). Research currently indicates that disulphide bond formation can occur via multiple parallel pathways where a large number of protein families may play a role in supplying redox equivalents. Furthermore, late-stage isomerization reactions, where disulphide bond formation is commonly linked to conformational changes in protein substrates that possess significant secondary structures, are thought to be catalysed by members of the protein disulphide isomerase (PDI) family.. Several proteins with similarity to PDI have been described in the ER of higher eukaryotes. The precise in vivo functions of these proteins remain elusive and the question arises why there are different members of the PDI family present in the same intracellular compartment. One inevitable speculation is that they have overlapping biological functions with their distinct roles only coming into effect under specific conditions, but this has not to date been systematically examined. Caenorhabditis elegans contains a full set of proteins with high homology to the mammalian members of the PDI family and to members of other protein families actively involved in disulphide redox reactions and thus, is invaluable as a eukaryotic model system for their biological and biochemical characterisation.. We report here on the RNAi analysis of members of the PDI family and of other proteins involved in disulphide bond formation in a multicellular organism. In addition, biochemical characterization of the major members of the PDI family in C. elegans, coupled with analysis of loss-of-function phenotypes (either RNAi-induced or based on genomic knockouts), strongly indicates an overlap in substrate specificities and, potentially, functions.. I would like to thank the Alexander S. Onassis Public Benefit Foundation for awarding me with a scholarship for the duration of this project.