Regulation of the Odorant Receptor ODR-10 via Endoplasmic Reticulum-Associated Degradation in Caenorhabditis elegans

The study of protein degradation mechanisms in neurons can advance our understanding of multiple neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. Endoplasmic reticulum-associated degradation (ERAD), plays an important role in reducing ER stress by degrading accumulating misfolded proteins, which in turn prevents cell death. Many proteins involved in ERAD are known, but the mechanisms themselves and roles of the proteins are not yet fully understood. We use the nematode Caenorhabditis elegans as a model for studying ERAD mechanisms. In particular our research focuses on the ubiquitin-proteasome system (UPS) in ERAD. Ubiquitin-proteasome systems have the ability to modify proteins and target them for degradation. Our goal is to help determine the relationship of the E2 and E3 ligase proteins of ERAD in neurons by studying the regulation of the transmembrane olfactory receptor ODR-10, in the AWA neurons of C. elegans. The ubiquitin pathway in ERAD involves multiple ubiquitin ligases (E2s and E3s). The interactions between the E2 and E3 enzymes, and their target specificity in the endoplasmic reticulum is not well understood in metazoan systems. Our research highlights the role and interactions of the E2 and E3 proteins with regards to regulation of ODR-10. We have analyzed the effects of loss of function mutations of E2 and E3 proteins to determine their effects on localization, expression levels of ODR-10, and also behavioral changes. Based upon this data we can make inferences of potential E2 and E3 protein interactions. Researching ODR-10 ubiquitin regulation in ERAD will enable us to further understand protein regulation in neurons. Through characterizing pathways that reduce cell stress, such as ERAD, we may even gain insight as to potential limits or treatments of neurodegenerative diseases.