Regulation of Autophagy by the Unfolded Protein Response

Autophagy is a highly conserved cellular response which allows the cell to degrade and recycle cellular proteins in an orderly manner. During autophagy cellular components are assembled into membrane-enclosed autophagasomes, which eventually fuses with the lysosome for degradation of the enclosed components. Under stressful or starvation conditions autophagy is activated as a cellular survival mechanisms, supplying essential nutrients required for cell survival. Misregulation of autophagy has been linked to human health, especially neurogenerative diseases. In this work, we focused on the cross-talk between the Unfolded Protein Response and Autophagy. The Unfolded Protein Response (UPR) is a cellular stress response that responds to the accumulation of unfolded proteins in the endoplasmic reticulum (ER). The UPR results in the increase in the protein folding capacity of the ER, increased degradation of unfolded proteins and a decrease in protein synthesis. Our lab focuses on two proteins that inhibit one branch of UPR signaling, called GADD34 and CReP. Using a yeast two-hybrid screen we identified novel CReP binding proteins, all of which are linked to autophagy. We hypothesized that GADD34 and CReP function to mechanistically link UPR and Autophagy signaling. We confirmed the protein-protein interactions between CReP and the novel binding partners using co-immunoprecipitations. In addition, we have established assays for autophagy using GFP-tagged LCIII a key marker of autophagy. Once concluded, this research will lead to a better mechanistic understanding of the links between autophagy and UPR