The secretory pathway is fundamental for majority of cellular responses in eukaryotes. Most secretory proteins are folded and modified in the endoplasmic reticulum (ER). Thus, the ER is critical for operation of the secretory pathway. To adjust protein-folding capacity in the ER, eukaryotic cells activate intra-cellular signaling pathways termed the unfolded protein response (UPR). The UPR is triggered by ER transmembrane sensors on ER stress, a cellular condition referring to the accumulation of unfolded proteins in the ER. To identify the plant UPR regulators, I performed mutant analyses of a conserved ER stress sensor IRE1 in Arabidopsis. I established that IRE1 is a functional ER stress sensor in plants. By showing that an ire1 mutant displays a short-root phenotype under normal growth conditions, I revealed a biological function of plant IRE1 in multicellular organisms. In addition, I found that a mutant of a component of G-protein complex, AGB1, enhances both the ER stress-sensitive and the short-root phenotype in ire1, suggesting that regulation of AGB1 on the UPR does not completely rely on IRE1. I further investigated regulatory relationship between the UPR and other cellular processes. Auxin is a major phytohormone essential for plant physiology. I found that ER stress down-regulates the transcription of auxin receptors and transporters, suggesting that ER stress represses the auxin response to coordinate stress adaption and growth regulation. By establishing that ER-localized auxin transporters and regulators are required for optimal UPR activation, I uncovered a previously unknown cellular function of ER-based auxin biology. The results also support the suggestion that regulation on auxin homeostasis is a plant-specific strategy to cope with ER stress. Moreover, I showed that ire1 displays a compromised root-inhibition phenotype under exogenous auxin treatment, indicating that IRE1 is required for the auxin response. The free auxin level is lower in ire1, supporting a role of IRE1 in regulation of the auxin homeostasis. I further examined the functional relationship between IRE1 and an ER-localized auxin transporter, PIN5. I found that pin5 enhances the defects of both the auxin response and the UPR activation in ire1. Together, my results have established the inter-regulation of the UPR and auxin signaling. In summary, my work has identified a conserved ER stress sensor IRE1 and previously unknown UPR regulators, ER-localized auxin regulators. By examination of the regulatory relationship between IRE1 and AGB1 or PIN5, my results contribute to important understanding of the plant UPR signaling network. I have also uncovered biological roles of plant IRE1 in primary root growth and auxin homeostasis. Thus, I have provided significant insights into regulators and physiological significance of the plant UPR.
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