UC San Diego

The endoplasmic reticulum (ER) is an essential organelle responsible for protein synthesis and modification. Since the ER is crucial for protein synthesis it has evolved multiple quality control pathways that monitor and respond to developmental and environmental cues that demand increased ER function. When the ER experiences increased demands for protein folding and modifications, quality control pathways such as the unfolded protein response (UPR) and the ER surveillance (ERSU) pathways have emerged. Malfunction of the ER quality control responses leads to multiple diseases such as Alzheimer's disease, obesity, and asthma. The aim of this investigation was to characterize the UPR in the absence of Aux1, a protein previously discovered to associate with the ER and to act as a component of cortical ER inheritance. In cells lacking Aux1, the splicing kinetics of HAC1 mRNA showed a faster attenuating UPR response compared to wild type cells. This faster attenuating response correlated with faster attenuation of KAR2 mRNA levels and Ire1 foci formation. The luminal state of the ER, monitored by Kar2/ BiP mobility, demonstrated that the faster attenuating UPR response in aux1[Delta] cells was due to less unfolded proteins. Lower amounts of unfolded proteins in the lumen of aux1[Delta] cells was not due to fewer overall proteins but instead was in part due to a more efficient ER- associated degradation (ERAD) pathway. Ultimately, although the role of Aux1 is still under investigation, Aux1 may be a component of a pre-quality control pathway responsible for monitoring proteins into the ER lumen