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Williams, B, Kabbage, M, Britt, R and Dickman, MB (2010) AtBAG7, an Arabidopsis Bcl-2-associated athanogene, resides in the endoplasmic reticulum and is involved in the unfolded protein response. Proc. Natl. Acad. Sci. U.S.A. 107:6088-93
The Bcl-2-associated athanogene (BAG) family is an evolutionarily conserved, multifunctional group of cochaperones that perform diverse cellular functions ranging from proliferation to growth arrest and cell death in yeast, in mammals, and, as recently observed, in plants. The Arabidopsis genome contains seven homologs of the BAG family, including four with domain organization similar to animal BAGs. In the present study we show that an Arabidopsis BAG, AtBAG7, is a uniquely localized endoplasmic reticulum (ER) BAG that is necessary for the proper maintenance of the unfolded protein response (UPR). AtBAG7 was shown to interact directly in vivo with the molecular chaperone, AtBiP2, by bimolecular fluorescence complementation assays, and the interaction was confirmed by yeast two-hybrid assay. Treatment with an inducer of UPR, tunicamycin, resulted in accelerated cell death of AtBAG7-null mutants. Furthermore, AtBAG7 knockouts were sensitive to known ER stress stimuli, heat and cold. In these knockouts heat sensitivity was reverted successfully to the wild-type phenotype with the addition of the chemical chaperone, tauroursodexycholic acid (TUDCA). Real-time PCR of ER stress proteins indicated that the expression of the heat-shock protein, AtBiP3, is selectively up-regulated in AtBAG7-null mutants upon heat and cold stress. Our results reveal an unexpected diversity of the plant's BAG gene family and suggest that AtBAG7 is an essential component of the UPR during heat and cold tolerance, thus confirming the cytoprotective role of plant BAGs.
Arabidopsis/genetics; Arabidopsis/metabolism; Arabidopsis Proteins/genetics; Arabidopsis Proteins/metabolism; Cold Temperature; Cryoprotective Agents/metabolism; Endoplasmic Reticulum/metabolism; Genes, Plant; Genetic Complementation Test; Hot Temperature; Molecular Chaperones/genetics; Molecular Chaperones/metabolism; Multigene Family; Mutation; Stress, Physiological; Tunicamycin/pharmacology; Two-Hybrid System Techniques; Unfolded Protein Response/drug effects; Unfolded Protein Response/genetics; Unfolded Protein Response/physiology; Up-Regulation