NIH Postdoctoral Fellow Rice University Rosharon, Texas
Across eukaryotic organisms, perturbations such as developmental transitions or stressors can cause the molecular needs of it’s cells to change and may require a shift in the proteome to address the new conditions. As the endoplasmic reticulum (ER) is the site of synthesis and folding for roughly one-third of the cellular proteome, this proteomic shift can produce a sharp increase in nascent peptides being loaded into the ER that require proper folding. When this overwhelms the folding capacity of the ER and results in the accumulation of misfolded proteins, this is known as ER stress, which is cytotoxic to the cell and can compromise the health of the organism. The unfolded protein response (UPR) is a pathway cells employ to sense and respond to ER stress. Early stages of the UPR are centered around alleviating the stress, but prolonged ER stress will cause the UPR to transition to cell-death measures. Arabidopsis thaliana provides a strong platform for studying the UPR because viable mutants of the major branches of the pathway can be generated and used for experimentation. These mutants show dramatic phenotypes in ER stress conditions and have allowed us to use ethyl methanesulfonate mutagenesis to identify proteins involved in death promoting mechanisms during ER stress. We have identified critical proteins that are involved in cell-fate determination during response to ER stress in A. thaliana. To date, their characterization has revealed new molecular players in the UPR and exciting new avenues of investigation into the pro-death side of response to ER stress.