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Date of Graduation
Master of Science (MS)
Department of Biology
The nascent polypeptide-associated complex (NAC) is a highly conserved protein complex known to play an important role in the development of metazoan organisms, but its molecular function is not well understood. Recent evidence from experiments using Saccharomyces cerevisiae as model supported the hypothesis that the NAC is either a chaperone or a component of the cytosolic chaperone network that interacts with nascent peptides emerging from the ribosome. We tested this model in C. elegans and found that the homologues of the NAC , icd-1 and icd-2, behave like chaperones in the worm. Lack of icd-1 or icd-2 altered the worms stress response to heat and led to a dramatic up-regulation of hsp-4; the homologue of the human ER chaperone BiP. Worms lacking the ER stress signalling protein xbp-1 generated a higher proportion of defective embryos and had a lower survival rate compared to wildtype populations during icd-1(RNAi). Furthermore, icd-1(RNAi) increased the size of lysosomes in wildtype worms and embryo gut cells, indicating an up-regulation of ER-mediated autophagy. These results suggest that disruption of the NAC by RNAi causes ER stress in the worm and is likely the cause of embryonic apoptosis that was previously observed in the worm.
Arsenovic, Paul T., "The role of the nascent polypeptide-associated complex in Caenorhabditis elegans" (2011). Masters Theses, 2010-2019. 134.