The UPR branch IRE1-bZIP60 in plants plays an essential role in viral infection and is complementary to the only UPR pathway in yeast.

Lingrui Zhang,Federica Brandizzi,Jeanmarie Verchot,Hui Chen,Aiming Wang,Karolina M Pajerowska-Mukhtar

doi:10.1371/journal.pgen.1005164

Abstract

The unfolded protein response (UPR) signaling network encompasses two pathways in plants, one mediated by inositol-requiring protein-1 (IRE1)-bZIP60 mRNA and the other by site-1/site-2 proteases (S1P/S2P)-bZIP17/bZIP28. As the major sensor of UPR in eukaryotes, IRE1, in response to endoplasmic reticulum (ER) stress, catalyzes the unconventional splicing of HAC1 in yeast, bZIP60 in plants and XBP1 in metazoans. Recent studies suggest that IRE1p and HAC1 mRNA, the only UPR pathway found in yeast, evolves as a cognate system responsible for the robust UPR induction. However, the functional connectivity of IRE1 and its splicing target in multicellular eukaryotes as well as the degree of conservation of IRE1 downstream signaling effectors across eukaryotes remains to be established. Here, we report that IRE1 and its substrate bZIP60 function as a strictly cognate enzyme-substrate pair to control viral pathogenesis in plants. Moreover, we show that the S1P/S2P-bZIP17/bZIP28 pathway, the other known branch of UPR in plants, does not play a detectable role in virus infection, demonstrating the distinct function of the IRE1-bZIP60 pathway in plants. Furthermore, we provide evidence that bZIP60 and HAC1, products of the enzyme-substrate duet, rather than IRE1, are functionally replaceable to cope with ER stress in yeast. Taken together, we conclude that the downstream signaling of the IRE1-mediated splicing is evolutionarily conserved in yeast and plants, and that the IRE1-bZIP60 UPR pathway not only confers overlapping functions with the other UPR branch in fundamental biology but also may exert a unique role in certain biological processes such as virus-plant interactions.

Highlights

The accumulation of unfolded protein in the endoplasmic reticulum (ER) results in ER stress that triggers the unfolded protein response (UPR), a complex signal transduction cascade that orchestrates adaptation to ER stress or induces apoptosis if ER stress remains unmitigated [1,2,3,4,5,6]
Given that all eukaryotes are equipped with the inositol-requiring protein-1 (IRE1)-mediated pathway, are IRE1 downstream signaling effectors conserved among kingdoms and at what degree? Here, we show that IRE1 and its substrate bZIP60 function as a matched enzyme-substrate pair to mediate virus-host interactions in plants
We demonstrate that the spliced form bZIP60 and HAC1p, rather than IRE1, are functionally replaceable to cope with abiotic stress in yeast, suggesting that the downstream signaling of the IRE1-mediated splicing is evolutionary conserved in plants and yeast

Summary

Introduction

The accumulation of unfolded protein in the endoplasmic reticulum (ER) results in ER stress that triggers the unfolded protein response (UPR), a complex signal transduction cascade that orchestrates adaptation to ER stress or induces apoptosis if ER stress remains unmitigated [1,2,3,4,5,6]. The UPR is mediated by three classes of membrane-associated sensor transducers including inositol-requiring transmembrane kinase/endonuclease (IRE1), protein kinase RNA (PKR)-like ER kinase (PERK), and activating transcription factor 6 (ATF6) [2,3]. The UPR in yeast is controlled by only the IRE1p-mediated signaling pathway, which triggers the expression of over 5% genes mainly encoding chaperones and ER-associated protein degradation components in the genome [7]. Upon sensing ER stress, IRE1 dimerizes or oligomerizes in the plane of the ER membrane through the binding of unfolded proteins to its UPR sensor domain or the release of oligomerization-repressing chaperones, or both, allowing for trans-autophosphorylation of juxtaposed kinase domains [8,9,10]. Based on the crystal structure of the dual catalytic region of IRE1, the trans-autophosphorylation of the kinase domain of IRE1 is suggested to permit unfettered binding to nucleotides (nt), which in turn promotes dimerization of IRE1 to compose the active ribonuclease site, unmasking the dormant endoribonucleolytic activity [3,11]

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