AtBAG7 , an Arabidopsis Bcl-2–associated athanogene, resides in the endoplasmic reticulum and is involved in the unfolded protein response

Abstract

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.programmed cell death | chaperones | cytoprotection

Aspartyl Protease-Mediated Cleavage of BAG6 Is Necessary for Autophagy and Fungal Resistance in Plants

“…In particular, human and plant BAG proteins show high degrees of structural conservation in the functional portions of the protein (e.g., helical structure and hydrophobicity; Doukhanina et al, 2006) that when taken together account for functional similarity. In accordance, our studies have indicated that plant BAG family members are also multifunctional and similar to their animal counterparts, as they block several biotic and abiotic cell death-mediated processes while conferring cytoprotection in situations ranging from pathogen attack to drought stress to plant development (Doukhanina et al, 2006;Williams et al, 2010).…”

“…The BAG genes constitute a broadly conserved gene family and function as adapter proteins/cochaperones, forming complexes with signaling molecules and molecular chaperones including Hsp70 (Kabbage and Dickman, 2008;Williams et al, 2010). In mammals, BAG proteins are associated with several key cellular processes, including apoptosis, autophagy, proliferation, differentiation, and stress signaling (Takayama et al, 1999;Song et al, 2001).…”

“…family, it appears that these family members have adapted to particular niches/locations for selected functions (Doukhanina et al, 2006;Kabbage and Dickman, 2008;Williams et al, 2010). It is these functions and how they are regulated that are of major interest.…”

“…Arabidopsis BAG6 was previously shown to be associated with calmodulin and calmodulin-dependent signaling (Kang et al, 2006). BAG7, an ER-localized BAG member, is involved with the unfolded protein response as a result of ER stress, and the deletion of BAG7 compromises heat and cold tolerance (Williams et al, 2010). Interestingly, we recently determined that BAG7 is also processed and, as a result, translocates from the ER to the nucleus where it interacts with the WRKY29 transcription factor resulting in an abiotic stress tolerant phenotype (Y. Li and M.B.…”

“…The remaining three members contain a predicted calmodulin binding motif near the BAG domain, a feature unique to plant BAG proteins indicating possible divergent mechanisms associated with plantspecific functions. As noted for mammalian BAGs, plant BAGs also regulate several stress and developmental processes (Kabbage and Dickman, 2008;Williams et al, 2010). Thus structural approaches can be used for prediction of protein function independent of sequence similarity.…”