Abstract
BINDING PROTEIN (BiP) is a major chaperone in the endoplasmic reticulum (ER) lumen, and this study shows that BiP binds to the C-terminal tail of the stress sensor/transducer bZIP28, a membrane-associated transcription factor, retaining it in the ER under unstressed conditions. In response to ER stress, BiP dissociates from bZIP28, allowing it to be mobilized from the ER to the Golgi where it is proteolytically processed and released to enter the nucleus. Under unstressed conditions, BiP binds to bZIP28 as it binds to other client proteins, through its substrate binding domain. BiP dissociates from bZIP28 even when bZIP28's exit from the ER or its release from the Golgi is blocked. Both BiP1 and BiP3 bind bZIP28, and overexpression of either BiP detains bZIP28 in the ER under stress conditions. A C-terminally truncated mutant of bZIP28 eliminating most of the lumenal domain does not bind BiP and is not retained in the ER under unstressed conditions. BiP binding sites in the C-terminal tail of bZIP28 were identified in a phage display system. BiP was found to bind to intrinsically disordered regions on bZIP28's lumen-facing tail. Thus, the dissociation of BiP from the C-terminal tail of bZIP28 is a major switch that activates one arm of the unfolded protein response signaling pathway in plants.
Highlights
BINDING IMMUNOGLOBULIN PROTEIN, or Binding Protein (BiP), known in animal systems as 78-kD Glc-regulated protein or heat shock 70-kD protein 5, and calnexin/calreticulin are the two major chaperone systems in the endoplasmic reticulum (ER) lumen (Otero et al, 2010)
To determine if we could further restrain the stress mobilization of YFP-bZIP28 by preventing its dissociation from BiP, we introduced into Arabidopsis mutated forms of BiP (BiPG235D) that are known in other systems to interfere with ATP binding and the release of client proteins
Our results show that BiP binds to bZIP28 under unstressed conditions and appears to bind to it in the same manner as it does to other client proteins, such as CPY*
Summary
BINDING IMMUNOGLOBULIN PROTEIN, or Binding Protein (BiP), known in animal systems as 78-kD Glc-regulated protein or heat shock 70-kD protein 5, and calnexin/calreticulin are the two major chaperone systems in the endoplasmic reticulum (ER) lumen (Otero et al, 2010). BiPs form complexes with the HSP40-like cochaperones containing J domains (ERdj3) and stromal-derived factor-2 (Jin et al, 2008; Nekrasov et al, 2009; Schott et al, 2010). These BiP complexes maintain nascent proteins in a competent state for subsequent folding and oligomerization (Anelli and Sitia, 2008). BiP plays an important role in the unfolded protein response (UPR) by regulating stress transducers, such as ACTIVATING TRANSCRIPTION FACTOR6 (ATF6), Protein kinase RNA-like ER kinase, and Inositol Requiring Enzyme (IRE1) in animal cells (Bertolotti et al, 2000; Shen et al, 2002). BiP and ATF6 rapidly dissociate, and ATF6 becomes a cargo in the ER-to-Golgi trafficking system (Shen et al, 2002). Shen et al (2002) observed that BiP binds to three regions in the lumenal
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