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Date of Graduation
Master of Science (MS)
Department of Biology
Timothy Alan Bloss
The nascent polypeptide-associated complex (NAC) is a highly conserved heterodimer known to play an important role in protein folding and localization during metazoan development. Evidence in different model systems indicates that removal of either subunit of the NAC, i.e. α- or β-NAC, is sufficient to generate misfolded protein stress in the endoplasmic reticulum (ER), resulting in the activation of the ER-specific unfolded protein response (UPR). What is not yet understood is the nature of the UPR depending on which subunit of the NAC is depleted. My research is focused on characterizing the specific UPR outcomes induced upon depletion of either α- or β-NAC during misfolded protein stress in the ER. Assessment of UPR outcomes revealed that depletion of the C. elegans NAC homologues icd-1/NAC and icd-2/NAC shared unique responses relative to the subunit depleted. Specifically, depletion of ICD-1 led to increased ER specific chaperone expression and robust attenuation of protein synthesis when compared to depletion of ICD-2. Along with managing protein homeostasis during ER stress, I also found that specific components of the NAC and UPR actively contribute to cell differentiation programs, e.g. embryos depleted of ICD-1 displayed altered neuronal marker expression during ER stress, while other cell-type specific markers remained unchanged. These results suggest the individual subunits of the C. elegans NAC are functional when unbound and contribute differentially to the activation of the UPR when one subunit is in excess relative to the other. Such findings may provide insights into the pathology of diseases such as Alzheimer’s, in which the 1:1 stoichiometry of the NAC subunits is disrupted.
Sandoval, Jonathan E., "Characterization of the C. elegans nascent polypeptide associated complex (NAC) function under stress" (2015). Masters Theses, 2010-2019. 56.