Plant cytoplasmic GAPDH: redox post-translational modifications and moonlighting properties

Abstract

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a ubiquitous enzyme involved in glycolysis and shown, particularly in animal cells, to play additional roles in several unrelated non-metabolic processes such as control of gene expression and apoptosis. This functional versatility is regulated, in part at least, by redox post-translational modifications that alter GAPDH catalytic activity and influence the subcellular localization of the enzyme. In spite of the well established moonlighting (multifunctional) properties of animal GAPDH, little is known about non-metabolic roles of GAPDH in plants. Plant cells contain several GAPDH isoforms with different catalytic and regulatory properties, located both in the cytoplasm and in plastids, and participating in glycolysis and the Calvin-Benson cycle. A general feature of all GAPDH proteins is the presence of an acidic catalytic cysteine in the active site that is overly sensitive to oxidative modifications, including glutathionylation and S-nitrosylation. In Arabidopsis, oxidatively modified cytoplasmic GAPDH has been successfully used as a tool to investigate the role of reduced glutathione, thioredoxins and glutaredoxins in the control of different types of redox post-translational modifications. Oxidative modifications inhibit GAPDH activity, but might enable additional functions in plant cells. Mounting evidence support the concept that plant cytoplasmic GAPDH may fulfill alternative, non-metabolic functions that are triggered by redox post-translational modifications of the protein under stress conditions. The aim of this review is to detail the molecular mechanisms underlying the redox regulation of plant cytoplasmic GAPDH in the light of its crystal structure, and to provide a brief inventory of the well known redox-dependent multi-facetted properties of animal GAPDH, together with the emerging roles of oxidatively modified GAPDH in stress signaling pathways in plants.

Modulation of Protein S-Nitrosylation by Isoprene Emission in Poplar

“…Out of the group of CBB cycle enzymes, only TPI and Rubisco have been biochemically characterized, and both appeared to be inhibited by S-nitrosylation (Abat et al, 2008;Abat and Deswal, 2009;Zaffagnini et al, 2014). The cytosolic GAPDH was reported to be inhibited by S-nitrosylation as well (Holtgrefe et al, 2008;Zaffagnini et al, 2013). However, it is unclear if this is true for the chloroplastic GAPDH, which shares only low structural similarity with the cytosolic isoenzyme (Shih et al, 1991).…”

Cytoplastic Glyceraldehyde-3-Phosphate Dehydrogenases Interact with ATG3 to Negatively Regulate Autophagy and Immunity in Nicotiana benthamiana

“…Interestingly, GAPDH interacts with mammalian RNA binding protein p54nrb (54-kD nuclear RNA binding protein) in the cytosol in a manner dependent on the dose of H 2 O 2 to exert a potential role in transcription or replication (Hwang et al, 2009). In plants, GAPCs are identified as the direct inhibition targets of H 2 O 2 (Hancock et al, 2005;Holtgrefe et al, 2008;Zaffagnini et al, 2013). GAPCs could also respond to ROS signals by regulating their interacting partner proteins.…”

A light switch based on protein S-nitrosylation fine-tunes photosynthetic light-harvesting in the microalga Chlamydomonas reinhardtii

“…In addition, triose phosphate metabolites exported from the chloroplast and produced in a lightdependent manner by the Calvin-Benson cycle could also contribute to the interorganellar cross talk. Indeed, the cytosol contains a nonphosphorylating glyceraldehyde-3-phosphate dehydrogenase that oxidizes G3P directly to 3-phosphoglycerate and NADPH (Rius et al, 2006;Zaffagnini et al, 2013a). These shuttles could alter the redox state of the cytosol by increasing both the NADH/NAD + and NADPH/ NADP + ratio, which would result in increased availability of reduced thioredoxin h1 required for the denitrosylation of NAB1.…”