JXB Advance Access originally published online on May 19, 2006
Journal of Experimental Botany 2006 57(8):1777-1784; doi:10.1093/jxb/erj211
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
RESEARCH PAPER |
S-Nitrosylation: an emerging redox-based post-translational modification in plants
Institute of Molecular Plant Sciences, School of Biological Sciences, University of Edinburgh, King's Buildings, Edinburgh EH9 3JH, UK
*To whom correspondence should be addressed. E-mail: gloake{at}ed.ac.uk
Received 3 March 2006; Accepted 23 March 2006
 |
Abstract |
|---|
Top
Abstract
IntroductionS-nitrosylation, the covalent attachment of a nitric oxide moiety to a cysteine thiol, is now established as a key post-translational modification in animals. This process has been shown to regulate the function of a wide variety of regulatory, structural, and metabolic proteins. The emerging evidence now suggests that S-nitrosylation may also have a central function in plant biology.
Key words: Nitric oxide, plant disease resistance, redox signalling, S-nitrosothiols, S-nitrosylation
|
Introduction |
|---|
The discovery of the biological functions of nitric oxide (NO) in the late 1980s came as an unexpected surprise. Subsequently, NO was named ‘Molecule of the Year’ in 1992 by the journal Science. Furthermore, in 1998, Murad, Furchgott, and Ignarro shared the Nobel Prize for Physiology and Medicine for their work demonstrating that NO generated by endothelial cells relaxes smooth muscle through activation of guanylate cyclase (Murad, 1986). Gradually, the diverse cellular activities of NO, one of only a handful of gaseous signalling molecules, began to be appreciated. Early findings suggested that NO was a freely diffusible second messenger, with a promiscuous sphere of influence, functioning predominantly through the regulation of guanylate cyclase (Lancaster, 1994). More recent evidence, however, has resulted in a critical reappraisal of this initial paradigm, as NO signalling was increasingly found to occur independently of this key regulatory enzyme. The rich redox and additive chemistry of NO facilitates its interactions with centres of iron–sulphur clusters and haem, present in a wide variety of proteins, impacting their activities (Stamler, 1994). In 1992, an additional mechanism underpinning NO signalling was established: in this scenario, NO could be coupled to a reactive cysteine thiol, forming an S-nitrosothiol (SNO) (Stamler et al., 1992). The presence of this group could subsequently modulate protein function, analogous to the addition of a phosphate group during phosphorylation. Over the last decade, S-nitrosylation has been demonstrated to regulate an increasing number of signalling systems, structural proteins, and metabolic processes in animals (Hess et al., 2005). There is also a developing appreciation of the precise spatial and temporal regulation of SNO formation, which confers an exquisite specificity to NO signalling (Stamler et al., 1997). S-Nitrosylation has now become established as the prototypic, redox-based, post-translational modification within the animal sciences. However, the functions of SNO synthesis and turnover in plant biology are only just beginning to emerge. Thus, the early sections of this review will cover the role of S-nitrosylation in animal systems, with the final sections addressing the nascent field of SNO biology in plants.
|
S-Nitrosylation/de-nitrosylation/transnitrosylation |
|---|
The NO moiety required for S-nitrosylation can be derived from a diversity of sources in addition to NO, including other NOx species, metal–NO complexes, peroxynitrite, nitrite, or SNOs (Fig. 1). To date, specific enzymatic mechanisms responsible for S-nitrosylation have not been identified; however, several enzymes are known to promote S-nitrosylation or de-nitrosylation reactions. For example, ceruloplasmin catalyses the S-nitrosylation of the proteoglycan, glypican, and it can also promote the formation of S-nitrosoglutathione (GSNO) from NO (Inoue et al., 1999). Thiol-to-thiol SNO formation, termed transnitrosylation, has also been reported. In this case, NO from S-nitrosohaemoglobin has been shown to be directly transferred to a neighbouring thiol on Band3, a haemoglobin-interacting protein (Pawloski et al., 2001). SNO turnover or de-nitrosylation can be mediated by thioredoxin, exemplified by a reversal of the NO-mediated inhibition of protein kinase C (Kahlos et al., 2003).
|
GSNO is formed rapidly in cells and body fluids following the interaction of NO with GSH, a major cellular antioxidant (Gaston et al., 1993). GSNO is a stable and mobile molecule and can therefore serve as a reservoir of NO bioactivity. Recently, an enzyme has been reported that turns over GSNO. This so-called GSNO reductase (GSNOR), first purified from Escherichia coli, is also thought to be important for the control of GSNO homeostasis in yeast and mice (Liu et al., 2001). The absence of GSNOR function increased GSNO and protein-SNO levels, even though GSNOR does not directly de-nitrosylate the latter. This observation suggests there is a dynamic equilibrium between low molecular weight thiols and protein-SNOs which is based on the transfer of NO between these species. In this context, GSNO can transfer NO to protein-thiols either by transnitrosylation or by providing NO in the presence of transition metals and reducing agents (Stubauer et al., 1999).
|
Specificity of protein S-nitrosylation |
|---|
Proteins exhibit a striking differential susceptibility to S-nitrosylation; however, in this respect, their overall content of cysteines is unimportant. It has become clear that S-nitrosylation occurs with exquisite specificity. Characteristically, proteins regulated by this process under physiological conditions are only S-nitrosylated on a specific cysteine residue that is both necessary and sufficient. The local pH, redox tone, or presence of metal ions, such as Mg2+ or Ca2+, which can all function as allosteric effectors to control thiol accessibility or reactivity, are significant determinants (Eu et al., 2000; Hess et al., 2001; Lai et al., 2001). Furthermore, electrostatic interactions that control thiol pKa or hydrophobic compartmentation are also thought to be important (Stamler, 1997; Hess et al., 2001). Elegant studies analysing the S-nitrosylation of haemoglobin at Cys93 demonstrated that oxygenation and deoxygenation of haemoglobin promote the S-nitrosylation and de-nitrosylation of Cys93, respectively. This was found to facilitate the delivery by red blood cells of vasodilatory NO bioactivity along with O2 to satisfy the cellular requirements determined by the local physiological environment (Funaia et al., 1997; James et al., 2004; Singel and Stamler, 2005). Importantly, Cys93 is flanked alternatively by basic and acidic side chains. This observation prompted the development of the ‘acid–base’ motif for S-nitrosylation (Stamler et al., 1997). Similar conserved structural features characteristically underpin other post-translational modifications, for example, protein phosphorylation. In the case of the SNO motif, it is especially noteworthy that the cysteine target may not be embedded between flanking acidic and basic residues in the primary protein sequence; such a juxtaposition may only be apparent following analysis of the three-dimensional structure (Stamler et al., 1997; Hess et al., 2001; Hao et al., 2006). This is exemplified by the S-nitrosylation of methionine adenosyltransferase (MAT; Perez-Mato et al., 1999). Furthermore, an SNO motif may also emerge from either the quaternary structure of the S-nitrosylated protein or following protein–protein interactions, as is the case for the transnitrosylation of Band3 by haemoglobin (Stamler et al., 1997). Also, this motif may only operate in hydrophilic environments, whereas NO function is important in membranes and other hydrophilic environments (Stamler et al., 1997). ‘Protein tunnels’ within and between proteins may also function as specificity determinants. These structures may direct the transfer of NO to the target cysteine residue, as described for the transfer of NO from the haem iron to the cysteine thiol of haemoglobin, by the conformation-dependent formation of a hydrophobic ‘xenon pocket’ (Chu et al., 2000).
Analysis of the S-nitrosylation of OxyR by GSNO has led to the proposal of a potential motif for GSNO-mediated protein S-nitrosylation (Hess et al., 2005). GSNO is thought to dock within the binding pocket for oxidized glutathione (GSSG). This is underpinned by hydrogen bonding between the 
-glutamyl amine of GSNO and the -carboxylate of Asp202. This may position the NO group within 
4 Å of the Cys199 sulphur moiety. A possible motif for trans-S-nitrosylation derived from the sequences around Cys199 has been proposed as (H,K,R)(C)(hydrophobic)(X)(D,E) where X is any amino acid. This motif, identified by database analysis, was found to be present in a number of vertebrate proteins that are substrates for S-nitrosylation.
Interestingly, a recent report describing the analysis of SNO cysteine sites in rat cerebellum proteins could find no evidence for a linear flanking motif that predicts the site of S-nitrosylation (Hao et al., 2006). Rather, 3D structural features are likely to be the sole determinants of specificity. In this context, it was found that 50% of the S-nitrosylated cysteine residues were in close proximity to aromatic amino acids, with cysteine sulphur pointing towards aromatic ring hydrogen atoms and apparently engaged in electrostatic interactions. This may provide a general structural motif that renders cysteine susceptible to S-nitrosylation.
Recently, a further important determinant of specificity has emerged: protein–protein interactions involving nitric oxide synthase (NOS), the enzymatic source of NO, designed to increase local NO concentrations in proximity to target thiols. In the case of Dexras1 and the N-methyl-D-aspartate receptor, NOS is co-localized by virtue of its interactions with the scaffold proteins CAPON and PSD95, respectively (Choi et al., 2000; Fang et al., 2000). Recently, a new variation on this theme has been uncovered with the demonstration that inducible NOS (iNOS) directly binds cyclo-oxygenase 2, the protein possessing the target thiol, driving the S-nitrosylation of Cys526, which results in the activation of this key inflammatory mediator (Kim et al., 2005).
|
Regulation of protein function by S-nitrosylation |
|---|
A rapidly increasing number of substrates for S-nitrosylation have been reported; these include protein kinases, phosphatases, ion channels, metabolic and regulatory enzymes, cytoskeletal and structural proteins, transcription factors, oxidoreductases, and respiratory proteins (Hess et al., 2005). Generally, where the target cysteine has been uncovered, S-nitrosylation is cognate to the control of either catalytic or regulatory activity.
Dimethylarginine dimethylaminohydrolases (DDAHs), required for arginine metabolism, possess a catalytic triad which contains an SNO motif (Leiper et al., 2002). The S-nitrosylation of this regulatory element at Cys249 has been shown to inhibit the activity of DDAH (Leiper et al., 2002). This catalytic triad is common to a variety of enzymes cognate to arginine metabolism including arginine glycine amidinotransferase and arginine deiminase. Furthermore, ornithine decarboxylase, which catalyses the formation of putrescine (a precursor for polyamine synthesis) from ornithine (the product of arginase), is inhibited by S-nitrosylation of the active site thiol (Bauer et al., 2001). Also, S-adenosylmethione decarboxylase (Hillarya and Pegg, 2003) and MAT, additional polyamine handling enzymes, are also regulated by S-nitrosylation (Perez-Mato et al., 1999). Collectively, these data highlight that the metabolic fate of arginine, the substrate for NO synthesis from NOSs, which includes polyamine biosynthesis, may be tightly regulated by S-nitrosylation.
The release of Ca2+ from the sarcoplasmic reticulum (SR), which controls muscle contraction, is predominantly controlled by the type 1 ryanodine receptor/Ca2+ ionophore (RyR1) of skeletal muscle. S-Nitrosylation has been shown to activate RyR1 in isolated SR vesicles (Eu et al., 2000). NO generated from neuronal NOS (nNOS) results in the S-nitrosylation of a single thiol at Cys3635, despite an abundance of free thiols in each RyR1 monomer. This regulatory thiol is embedded within the hydrophobic, calmodulin (CaM)-binding domain of RyR1 (Sun et al., 2001). Interestingly, S-nitrosylation at this site is controlled by O2 tension, which at high levels inhibits this process by acting as an allosteric regulator. Thus, Ca2+ flux and muscle contraction are promoted by NO signalling at physiological but not at elevated O2 levels (Eu et al., 2000).
|
NO function in plant biology |
|---|
NO has lately emerged as a key signalling molecule in plants which functions in a diverse array of cellular processes including: stomatal closure, seed germination, root development, senescence, flowering time, the activation of defence-related genes, and hypersensitive cell death (Guo et al., 2003; Neill et al., 2003; Romero-Puertas et al., 2004; Guo and Crawford, 2005). The mechanism(s) of NO synthesis underpinning these processes is also beginning to be resolved.
Unlike animals, archetypal NOSs are not found in plants, but recently a novel NOS, with sequence similarity to a protein implicated in NO synthesis in snails, has been uncovered (Guo et al., 2003). Other sources of NO include nitrate reductase (Desikan et al., 2002), non-enzymatic reactions (Bethke et al., 2004), and mitochondrial nitrite-dependent NO synthesis (Planchet et al., 2005). Exactly how these mechanisms of NO synthesis are integrated to orchestrate plant growth, development, and responses to the environment is not well understood. Furthermore, the principal effector mechanism(s) for NO-based regulation of cellular function in plants remains to be determined. As described above, S-nitrosylation has emerged as a key instrument in the expression of NO function in animals. However, the role, if any, of this post-translational regulatory mechanism in plant biology has remained, until recently, largely enigmatic.
|
Identification of plant S-nitrosothiols |
|---|
Most contemporary data underpinning S-nitrosylation are derived from in vitro studies utilizing purified or recombinant proteins investigated on a case-by-case basis. The development of biotin-switch technology, however, has now provided a more rapid entry point to the world of NO biology. This elegant approach, formulated in the Snyder laboratory, facilitates the rapid identification of S-nitrosylated proteins in situ as well as in vitro (Jaffrey et al., 2001). A three-step procedure is employed which converts S-nitrosylated cysteines into biotinylated cysteines. These proteins, which now possess biotin tags, are purified and subsequently identified by mass spectrometry. This technology was utilized to uncover 15 proteins from brain lysates that were specifically S-nitrosylated in vitro in response to various NO donors. Furthermore, this modification was absent in transgenic mice deleted for nNOS function (Jaffrey et al., 2001). A recent modification to this technology has been reported that facilitates the direct identification of the SNO cysteine sites within the uncovered SNOs (Hao et al., 2006).
The biotin-switch strategy has now been employed by a number of plant biology laboratories as a means to prime S-nitrosylation research (Romero-Puertas et al., 2004; Lindermayr et al., 2005; Y Wang, GJ Loake, unpublished data). For example, the Durner group identified 63 proteins from cell cultures and 52 proteins from Arabidopsis leaves that were specifically S-nitrosylated following exposure to NO donors in vitro or NO gas in vivo. Furthermore, the Delledonne and Loake groups have uncovered proteins that become specifically S-nitrosylated during the establishment of plant disease resistance (see the following section). Collectively, these studies have identified targets that include stress-related, metabolic, signalling, redox-related, and structural proteins. A highlight from the Durner study was the identification of a number of enzymes related to amino acid handling, suggesting an important role for NO and cognate S-nitrosylation in the control of cellular metabolism. This pioneering approach underscored the applicability and specificity of the biotin-switch procedure for the study of S-nitrosylation in plants.
An alternative bioinformatics approach has also been employed to uncover possible S-nitrosylation targets. Searching of the SwissProt database for the degenerate SNO motif [GSTCYNQ]-[KRHDE]-C-[DE] revealed 103 matches in 99 sequences from the Arabidopsis proteome (Huber and Hardin, 2004). This regulatory element was found to be located in proteins integral to cell signalling, transport, the cell cycle, and metabolism. Taken together, these complementary approaches have provided some interesting candidate proteins which may be regulated by S-nitrosylation. It is anticipated that these important initial observations will function as primers to drive further studies.
|
Mechanism of SNO turnover in plant biology |
|---|
As discussed earlier, the enzyme GSNOR is thought to play an important role in cellular SNO homeostasis (Liu et al., 2001). Recently, an Arabidopsis gene with sequence similarity to GSNOR has been identified (Feechan et al., 2005). This gene was previously shown to encode a glutathione-dependent formaldehyde dehydrogenase (Diaz et al., 2003). Analysis of the recombinant protein, expressed in E. coli, demonstrated strong GSNOR activity (Sakamoto et al., 2002). Furthermore, the identity of this gene product was confirmed via the functional complementation of a yeast strain deleted for GSNOR. Therefore, this enzyme, termed Arabidopsis thaliana GSNOR1 (AtGSNOR1) (Feechan et al., 2005), may regulate the formation and turnover of SNOs in plants.
A role for AtGSNOR1 in the control of cellular SNO levels has now been confirmed (Feechan et al., 2005). The impact of loss- (Atgsnor1-3) and gain-of-function (Atgsnor1-1) mutations in AtGSNOR1 on SNO homeostasis has recently been investigated. In the absence of AtGSNOR1, the levels of SNOs were significantly elevated both under ambient conditions and during the expression of disease resistance. In contrast, in Atgsnor1-1 plants, where AtGSNOR1 is overexpressed, SNO levels were strikingly reduced under these two diverse cellular environments. Thus, AtGSNOR1 controls the extent of global S-nitrosylation in Arabidopsis (Feechan et al., 2005).
|
A central role for S-nitrosothiols in plant disease resistance |
|---|
Plants have evolved a complex series of integrated defences to prevent microbial colonization. Non-host disease resistance (NHR) provides the primary shield against the vast majority of potential pathogens (Collins et al., 2003; Thordal-Christensen, 2003). Superimposed upon this is resistance (R) gene-mediated protection. This consists of a plethora of resistance (R) gene products, which recognize corresponding avirulence (avr) proteins in the pathogen, triggering a battery of protective responses (Dangl and Jones, 2001). Finally, basal resistance functions as the last line of defence, limiting the extent of infection from pathogens that have circumvented higher order defences (Glazebrook et al., 1996; Parker et al., 1996; Grant et al., 2003). In combination, these systems provide a highly effective bulwark against pathogen colonization.
The production of NO underpins these three key defence networks (Delledonne et al., 1998; Durner et al., 1998), with AtNOS1 (Guo et al., 2003) likely to be responsible for the majority of NO synthesis, because loss of AtNOS1 function abolished basal resistance against Pseudomonas syringae pv. tomato (Pst) DC3000, a virulent bacterial pathogen of Arabidopsis (Zeidler et al., 2004). This central requirement for NO suggested that S-nitrosylation may also play an important role in plant disease resistance. To address this question, the Loake group investigated the impact of loss- and gain-of-function mutations in AtGSNOR1 on plant–pathogen interactions.
To assess the possible role of SNO formation and turnover in NHR, these lines were challenged with the wheat powdery mildew fungus Blumeria graminis f.sp. tritici (Bgt) for which Arabidopsis is a non-host (Yun et al., 2003). Atgsnor1-3 plants supported increased growth of Bgt compared with wild-type and Atgsnor1-1 plants. Similar results were obtained for the non-host bacterium P. syringae pv. phaseolicola, a pathogen of bean. Thus, AtGSNOR1 function is required for optimum NHR against either fungal or bacterial pathogens (Feechan et al., 2005).
In a similar fashion, the impact of Atgsnor1 mutations on R gene-mediated resistance was assessed. Loss of Atgsnor1 function compromised protection established by both subclasses of the nucleotide-binding site and leucine-rich repeat (NBS-LRR) classes of R proteins that contain either coiled-coil or Toll interleukin-1 receptor domains, respectively. Furthermore, basal disease resistance against virulent PstDC3000 and the downy mildew pathogen, Hyaloperonospora parasitica (Noco2), was also compromised. Thus, SNO formation and turnover is required for multiple modes of plant disease resistance (Feechan et al., 2005).
The molecular basis of this phenomenon reflected a requirement for AtGSNOR1 in signalling through salicylic acid (SA), a small molecule that impinges on the expression of NHR, R gene-mediated, and basal resistance (Uknes et al., 1992; Delaney et al., 1994; Yun et al., 2003). Thus, the expression of the SA-dependent marker gene, Pathogenesis-Related (PR) 1, was accelerated in Atgsnor1-1 plants but delayed and reduced in the Atgsnor1-3 line during the expression of all of these defence systems. Interestingly, in the absence of AtGSNOR1, both SA accumulation and signalling were reduced, suggesting that S-nitrosylation may control nodes both upstream and downstream of SA accumulation. Alternatively, AtGSNOR1 may operate within an SA-dependent positive feedback loop (Shah, 2003; Feechan et al., 2005). Work is progressing to discriminate between these possibilities and to identify and characterize potential target proteins for S-nitrosylation which are integral to this process.
|
S-Nitrosylation of methionine adenosyltransferase |
|---|
MAT catalyses the biosynthesis of S-adenosylmethionine (AdoMet), the most important methyl donor in transmethylation reactions. Furthermore, AdoMet is a substrate for the biosynthesis of polyamines and the plant hormone ethylene. Interestingly, of the two MAT isoforms in mammals, only MAT1A is regulated by S-nitrosylation, in response to NO produced from iNOS (Avila et al., 1997). Thus, NO regulates the biosynthesis of AdoMet and the production of metabolites that are dependent on the presence of this key precursor. MAT1 was one of the SNOs identified via the biotin-switch technique in Arabidopsis following the application of GSNO to protein extracts (Lindermayr et al., 2005). While the activity of recombinant MAT1 was reduced by GSNO by
30%, the other two isoforms of MAT in Arabidopsis remain unaffected (Lindermayr et al., 2006). Site-directed mutagenesis and mass spectrometric analysis demonstrated that S-nitrosylation of Cys114 of MAT1 is responsible for the inhibition of MAT1 activity in response to GSNO. NO is thought to antagonize the function of ethylene in plant senescence. Thus, NO may prolong the post-harvest life of horticultural plants by inhibiting ethylene biosynthesis (Leshem and Haramaty, 1996). Further, NO is also known to reduce ethylene production in Arabidopsis cell cultures (Lindermayr et al., 2006). As AdoMet is a key ethylene precursor, NO may negatively regulate the biosynthesis of this plant hormone by inhibiting the activity of MAT1. In addition, NO inhibits increased ethylene production in carnation following the addition of 1-aminocyclopropane-1-carboxylic acid (ACC), a key ethylene precursor, implying that NO also inhibits ethylene production downstream of ACC. Furthermore, S-adenosylhomocysteinase and cobalamin-independent methionine synthase activity may also impact the methionine pool, and both of these enzymes have been found to be S-nitrosylated in vitro (Lindermayr et al., 2005). Thus, S-nitrosylation may regulate ethylene biosynthesis at multiple points.
|
SNO function in the hypersensitive response |
|---|
A conspicuous feature routinely associated with the establishment of R gene-mediated resistance is the plant hypersensitive response (HR), a genetically programmed cell death event, analogous to apoptosis in animals (Greenberg, 1997; Lam et al., 2001). Inhibition of NOS activity during attempted pathogen infection has been shown to compromise R gene-mediated disease resistance (Delledonne et al., 1998), thus underscoring a pivotal role for NO in this process and, by association, perhaps also S-nitrosylation. Application of the biotin-switch procedure (as discussed above) has now begun to uncover some important SNOs (Lindermayr et al., 2005; MC Romero-Puertas et al., unpublished data; Y Wang, GJ Loake, unpublished data). Peroxiredoxin E (PrxIIE) is an enzyme required for the turnover of hydrogen peroxide and peroxynitrite ONOO–, a reactive nitrogen species generated by the reaction of NO with O2–. Furthermore, a plant peroxiredoxin has been shown to complement the absence of the cognate homologue in yeast to convey protection against oxidative stress (Sakamoto et al., 2003).
Recently, PrxIIE has been shown to be S-nitrosylated during the development of R gene-mediated resistance (MC Romero-Puertas et al., unpublished data). PrxIIE can also be S-nitrosylated in vitro, which inhibits the activity of this enzyme with respect to H2O2 turnover. Analysis of transgenic Arabidopsis lines either lacking or overexpressing PrxIIE, however, revealed that S-nitrosylation of this enzyme is unlikely to control either H2O2 concentrations or cell death development during the onset of the HR. Conversely, in the absence of PrxIIE function, the amount of tyrosine nitration strikingly increased, whereas in PrxIIE-overexpressing lines, the level of this modification was decreased relative to that of wild-type plants. Thus, the extent of tyrosine nitration mediated by ONOO– during the HR is regulated by the S-nitrosylation of PrxIIE (Fig. 2).
|
A complementary study has also identified numerous proteins that become specifically S-nitrosylated during the establishment of R gene-mediated disease resistance (Y Wang, GJ Loake, unpublished data). Particularly conspicuous was salicylic acid-binding protein (SABP) 3, which has previously been demonstrated to be required for HR development triggered by PstDC3000(avrpto) (Slaymaker et al., 2002), and, as the name suggests, to bind the key plant immune system activator, SA (Uknes et al., 1992). The carbonic anhydrase (CA) activity of SABP3 is extremely sensitive to NO in vitro, but SA binding is relatively unaffected. Site-directed mutagenesis identified the site of S-nitrosylation as Cys280 (Y Wang, GJ Loake, unpublished data), which is embedded within a canonical SNO motif (Stamler et al., 1997). As loss of SABP3 function is thought to compromise HR formation (Slaymaker et al., 2002), S-nitrosylation of SABP3, inhibiting CA activity, may be part of a negative feedback loop to limit cell death development (Fig. 2). Significantly, the emerging pathology data also reveal that SABP3 plays an important role in disease resistance (Y Wang, GJ Loake, unpublished data). Thus, regulation of SABP3 function by S-nitrosylation may have a central role in the plant defence response.
|
Conclusions |
|---|
An increasing body of evidence has highlighted an important role for a variety of redox signalling mechanisms in the control of a plethora of cellular activities. Chief among these is S-nitrosylation, which has become established as the prototypic redox-based post-translational modification in animals. S-Nitrosylation is known to regulate the activity of a wide variety of proteins from ion channels to transcription factors that are integral to cell structure, signalling, and metabolism (Hess et al., 2005). Despite the abundance of protein thiols, this post-translational modification occurs with exquisite specificity, which is established by a variety of determinants including: allosteric regulators, thiol pKa, hydrophobic compartmentation, and interactions between NOSs and proteins targeted for S-nitrosylation (Hess et al., 2001).
The emerging evidence now suggests that this regulatory mechanism is also present in plants, where it may undertake important roles in the expression of multiple modes of plant disease resistance (Feechan et al., 2005; Y Wang, GJ Loake, unpublished data). Moreover, S-nitrosylation may also function in the control of hypersensitive cell death, which subserves the elimination of pathogen-infected host cells (B.-W. Yun and G. J. Loake, unpublished data). Tantalizing data also suggest an important role for S-nitrosylation in amino acid handling (C Lindermayr, J Durner, unpublished data). In the near future, it is possible that S-nitrosylation will be found to underpin the control of a large variety of cellular functions in plants. Furthermore, the application of the biotin-switch technique will enable an increasing number of the target cysteines, representing pivotal regulatory control points, to be uncovered. These data will provide an important platform to probe the molecular mechanisms underpinning these key post-translational modifications. It is anticipated that future advances in SNO biology may provide novel opportunities for both rational crop design and plant breeding potentially to improve a plethora of traits relevant to agriculture.
|
Acknowledgements |
|---|
We are grateful to those colleagues who provided unpublished data for this review. YW was supported by a Fellowship from the Royal Society, B-WY and EK are funded by the BBSRC, JY is the subject of an award from Brain Korea, and JKH is the recipient of a fellowship from the KRF. Work on S-nitrosylation in the Loake laboratory is funded by BBSRC grant BB/D011809/1.
|
Abbreviations |
|---|
ACC, 1-aminocyclopropane-1-carboxylic acid; AdoMet, S-adenosylmethionine; CA, carbonic anhydrase; DDAH, dimethylarginine dimethylaminohydrolase; GSNO, S-nitrosoglutathione; GSNOR, S-nitrosoglutathione reductase; HR, hypersensitive response; MAT, methionine adenosyltransferase; NHR, non-host disease resistance; NOS, nitric oxide synthase; PrxIIE, peroxiredoxin E; RyR1, type 1 ryanodine receptor; SABP3, salicylic acid-binding protein 3; SNO, S-nitrosothiol; SA, salicylic acid; SR, sarcoplasmic reticulum.
|
References |
|---|
Avila MA, Mingorance J, Martinez-Chantar ML, Casado M, Martin-Sanz P, Bosca L, Mato JM. (1997) Regulation of rat liver S-adenosylmethionine synthetase during septic shock: role of nitric oxide. Hepatology 25:391–396.[Web of Science][Medline]
Bauer PM, Buga GM, Fukuto JM, Pegg AE, Ignarro LJ. (2001) Nitric oxide inhibits ornithine decarboxylase via S-nitrosylation of cysteine 360 in the active site of the enzyme. Journal of Biological Chemistry 276:34458–34464.
Bethke PC, Badger MR, Jones RL. (2004) Apoplastic synthesis of nitric oxide by plant tissues. The Plant Cell 16:332–341.
Choi YB, Tenneti L, Le DA, Ortiz J, Bai G, Chen HS, Lipton SA. (2000) Molecular basis of NMDA receptor-coupled ion channel modulation by S-nitrosylation. Nature Neuroscience 3:15–21.[CrossRef][Web of Science][Medline]
Chu K, Vojtchovsky J, McMahon BH, Sweet RM, Berendzen J, Schlichting I. (2000) Structure of a ligand-binding intermediate in wild-type carbonmonoxy myoglobin. Nature 403:921–923.[CrossRef][Medline]
Collins NC, Thordal-Christensen H, Lipka V, et al. (2003) SNARE-protein-mediated disease resistance at the plant cell wall. Nature 425:973–977.[CrossRef][Medline]
Dangl JL and Jones JD. (2001) Plant pathogens and integrated defence responses to infection. Nature 411:826–833.[CrossRef][Medline]
Delaney TP, Uknes S, Vernooij B, Friedrich L, Weymann K. (1994) A central role of salicylic acid in plant disease resistance. Science 266:1247–1250.
Delledonne M, Xia Y, Dixon RA, Lamb C. (1998) Nitric oxide functions as a signal in plant disease resistance. Nature 394:585–588.[CrossRef][Medline]
Desikan R, Griffiths R, Hancock J, Neill S. (2002) A new role for an old enzyme: nitrate reductase-mediated nitric oxide generation is required for abscisic acid-induced stomatal closure in Arabidopsis thaliana. Proceedings of the National Academy of Sciences, USA 99:16314–16318.
Diaz M, Achkor H, Titarenko E, Martinez MC. (2003) The gene encoding glutathione-dependent formaldehyde dehydrogenase/GSNO reductase is responsive to wounding, jasmonic acid and salicylic acid. FEBS Letters 543:136–139.[CrossRef][Web of Science][Medline]
Durner J, Wendehenne D, Klessig DF. (1998) Defense gene induction in tobacco by nitric oxide, cyclic GMP, and cyclic ADP-ribose. Proceedings of the National Academy of Sciences, USA 95:10328–10333.
Eu J, Sun J, Xu L, Stamler J, Meissner G. (2000) The skeletal muscle calcium release channel coupled O2 sensor and NO signaling functions. Cell 102:499–509.[CrossRef][Web of Science][Medline]
Fang M, Jaffrey SR, Sawa A, Ye K, Luo X, Snyder SH. (2000) Dexras1: a G protein specifically coupled to neuronal nitric oxide synthase via CAPON. Neuron 28:183–193.[CrossRef][Web of Science][Medline]
Feechan A, Kwon E, Yun BW, Wang Y, Pallas JA, Loake GJ. (2005) A central role for S-nitrosothiols in plant disease resistance. Proceedings of the National Academy of Sciences, USA 102:8054–8059.
Funaia EFDA, Seligmana SP, Finlay TH. (1997) S-Nitrosohemoglobin in the fetal circulation may represent a cycle for blood pressure regulation. Biochemical and Biophysical Research Communications 239:875–877.[CrossRef][Web of Science][Medline]
Gaston B, Reilly J, Drazen JM, et al. (1993) Endogenous nitrogen oxides and bronchodilator S-nitrosothiols in human airways. Proceedings of the National Academy of Sciences, USA 90:10957–10961.
Glazebrook J, Rogers EE, Ausubel FM. (1996) Isolation of Arabidopsis mutants with enhanced disease susceptibility by direct screening. Genetics 143:973–982.[Abstract]
Grant JJ, Chini A, Basu D, Loake GJ. (2003) Targeted activation tagging of the Arabidopsis NBS-LRR gene, ADR1, conveys resistance to virulent pathogens. Molecular Plant–Microbe Interactions 16:669–680.[CrossRef]
Greenberg JT. (1997) Programmed cell death in plant–pathogen interactions. Annual Review of Plant Physiology and Plant Molecular Biology 48:525–545.[CrossRef][Web of Science][Medline]
Guo F-Q and Crawford NM. (2005) Arabidopsis nitric oxide synthase1 is targeted to mitochondria and protects against oxidative damage and dark-induced senescence. The Plant Cell 17:3436–3450.
Guo FQ, Okamoto M, Crawford NM. (2003) Identification of a plant nitric oxide synthase gene involved in hormonal signaling. Science 302:100–103.
Hao G, Derakhshan B, Shi L, Campagne F, Gross SS. (2006) SNOSID, a proteomic method for identification of cysteine S-nitrosylation sites in complex protein mixtures. Proceedings of the National Academy of Sciences, USA 103:1012–1017.
Hess DT, Matsumoto A, Kim SO, Marshall HE, Stamler JS. (2005) Protein S-nitrosylation: purview and parameters. Nature Review of Molecular Cell Biology 6:150–166.
Hess DT, Matsumoto A, Nudelman R, Stamler JS. (2001) S-Nitrosylation: spectrum and specificity. Nature Cell Biology 3:E46–E49.[CrossRef][Web of Science][Medline]
Hillarya R and Pegg AE. (2003) Decarboxylases involved in polyamine biosynthesis and their inactivation by nitric oxide. Biochimica et Biophysica Acta 1647:161–166.[Medline]
Huber SC and Hardin SC. (2004) Numerous posttranslational modifications provide opportunities for the intricate regulation of metabolic enzymes at multiple levels. Current Opinion in Plant Biology 7:318–322.[CrossRef][Web of Science][Medline]
Inoue K, Akaike T, Miyamoto Y, Okamoto T, Sawa T, Otagiri M, Suzuki S, Yoshimura T, Maeda H. (1999) Nitrosothiol formation catalyzed by ceruloplasmin. Implication for cytoprotective mechanism in vivo. Journal of Biological Chemistry 274:27069–27075.
Jaffrey SR, Erdjument-Bromage H, Ferris CD, Tempst P, Snyder SH. (2001) Protein S-nitrosylation: a physiological signal for neuronal nitric oxide. Nature Cell Biology 3:193–197.[CrossRef][Web of Science][Medline]
James PE, Tufnell-Barret T, Milsom AB, Frenneaux MP, Lang D. (2004) Red blood cell-mediated hypoxic vasodilatation: a balanced physiological viewpoint. Circulation Research 95:e8–e9.
Kahlos K, Zhang J, Block ER, Patel JM. (2003) Thioredoxin restores nitric oxide-induced inhibition of protein kinase C activity in lung endothelial cells. Molecular and Cellular Biochemistry 254:47–54.[CrossRef][Web of Science][Medline]
Kim SF, Huri DA, Snyder SH. (2005) Inducible nitric oxide synthase binds, S-nitrosylates, and activates cyclooxygenase-2. Science 310:1966–1970.
Lai TS, Hausladen A, Slaughter TF, Eu JP, Stamler JS, Greenberg CS. (2001) Calcium regulates S-nitrosylation, denitrosylation, and activity of tissue transglutaminase. Biochemistry 40:4904–4910.[CrossRef][Medline]
Lam E, Kato N, Lawton M. (2001) Programmed cell death, mitochondria and the plant hypersensitive response. Nature 411:848–853.[CrossRef][Medline]
Lancaster JR Jr. (1994) Simulation of the diffusion and reaction of endogeneously produced nitric oxide. Proceedings of the National Academy of Sciences, USA 91:8137–8141.
Leiper J, Murray-Rust J, McDonald N, Vallance P. (2002) S-nitrosylation of dimethylarginine dimethylaminohydrolase regulates enzyme activity: further interactions between nitric oxide synthase and dimethylarginine dimethylaminohydrolase. Proceedings of the National Academy of Sciences, USA 99:13527–13532.
Leshem YY and Haramaty E. (1996) The characterisation and contrasting effects of the nitric oxide free radical in vegetative stress and senescence of Pisum sativa Linn. foliage. Plant Physiology 148:258–263.
Lindermayr C, Saalbach G, Bahnweg G, Durner J. (2006) Differential inhibition of Arabidopsis methionine adenosyltransferases by protein S-nitrosylation. Journal of Biological Chemistry 281:4285–4291.
Lindermayr C, Saalbach G, Durner J. (2005) Proteomic identification of S-nitrosylated proteins in Arabidopsis. Plant Physiology 137:921–930.
Liu L, Hausladen A, Zeng M, Que L, Heitman J, Stamler JS. (2001) A metabolic enzyme for S-nitrosothiol conserved from bacteria to humans. Nature 410:490–494.[CrossRef][Medline]
Murad F. (1986) Cyclic guanosine monophosphate as a mediator of vasodilation. Journal of Clinical Investigation 78:1–5.[Web of Science][Medline]
Neill SJ, Desikan R, Hancock JT. (2003) Nitric oxide signalling in plants. New Phytologist 159:11–35.[CrossRef][Web of Science]
Parker JE, Holub EB, Frost LN, Falk A, Gunn ND, Daniels MJ. (1996) Characterization of eds1, a mutation in Arabidopsis suppressing resistance to Peronospora parasitica specified by several different RPP genes. The Plant Cell 8:2033–2046.[Abstract]
Pawloski JR, Hess DT, Stamler JS. (2001) Export by red blood cells of nitric oxide bioactivity. Nature 409:622–626.[CrossRef][Medline]
Perez-Mato I, Castro C, Ruiz FA, Corrales FJ, Mato JM. (1999) Methionine adenosyltransferase S-nitrosylation is regulated by the basic and acidic amino acids surrounding the target thiol. Journal of Biological Chemistry 274:17075–17079.
Planchet E, Jagadis Gupta K, Sonoda M, Kaiser WM. (2005) Nitric oxide emission from tobacco leaves and cell suspensions: rate limiting factors and evidence for the involvement of mitochondrial electron transport. The Plant Journal 41:732–743.[CrossRef][Web of Science][Medline]
Romero-Puertas MC, Perazzolli M, Zago ED, Delledonne M. (2004) Nitric oxide signalling functions in plant–pathogen interactions. Cellular Microbiology 6:795–803.[CrossRef][Web of Science][Medline]
Sakamoto A, Tsukamoto S, Yamamoto H, Ueda-Hashimoto M, Takahashi M, Suzuki H, Morikawa H. (2003) Functional complementation in yeast reveals a protective role of chloroplast 2-Cys peroxiredoxin against reactive nitrogen species. The Plant Journal 33:841–851.[CrossRef][Web of Science][Medline]
Sakamoto A, Ueda M, Morikawa H. (2002) Arabidopsis glutathione-dependent formaldehyde dehydrogenase is an S-nitrosoglutathione reductase. FEBS Letters 515:20–24.[CrossRef][Web of Science][Medline]
Shah J. (2003) The salicylic acid loop in plant defense. Current Opinion in Plant Biology 6:365–371.[CrossRef][Web of Science][Medline]
Singel DJ and Stamler JS. (2005) Chemical physiology of blood flow regulation by red blood cells. Annual Review of Physiology 67:99–145.[CrossRef][Web of Science][Medline]
Slaymaker DH, Navarre DA, Clark D, del Pozo O, Martin GB, Klessig DF. (2002) The tobacco salicylic acid-binding protein 3 (SABP3) is the chloroplast carbonic anhydrase, which exhibits antioxidant activity and plays a role in the hypersensitive defense response. Proceedings of the National Academy of Sciences, USA 99:11640–11645.
Stamler JS. (1994) Redox signaling: nitrosylation and related target interactions of nitric oxide. Cell 78:931–936.[CrossRef][Web of Science][Medline]
Stamler JS, Jia L, Eu JP, McMahon TJ, Demchenko IT, Bonaventura J, Gernert K, Piantadosi CA. (1997) Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen gradient. Science 276:2034–2037.
Stamler JS, Simon DI, Osborne JA, Mullins ME, Jaraki O, Michel T, Singel DJ, Loscalzo J. (1992) S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds. Proceedings of the National Academy of Sciences, USA 89:444–448.
Stamler JS, Toone EJ, Lipton SA, Sucher NJ. (1997) (S)NO signals: translocation, regulation, and a consensus motif. Neuron 18:691–696.[CrossRef][Web of Science][Medline]
Stubauer G, Giuffre A, Sarti P. (1999) Mechanism of S-nitrosothiol formation and degradation mediated by copper ions. Journal of Biological Chemistry 274:28128–28133.
Sun J, Xin C, Eu JP, Stamler JS, Meissner G. (2001) Cysteine-3635 is responsible for skeletal muscle ryanodine receptor modulation by NO. Proceedings of the National Academy of Sciences, USA 98:11158–11162.
Thordal-Christensen H. (2003) Fresh insights into processes of nonhost resistance. Current Opinion in Plant Biology 6:351–357.[CrossRef][Web of Science][Medline]
Uknes S, Mauch-Mani B, Moyer M, Potter S, Williams S, Dincher S, Chandler D, Slusarenko A, Ward E, Ryals J. (1992) Acquired resistance in Arabidopsis. The Plant Cell 4:645–656.
Yun BW, Atkinson HA, Gaborit C, Greenland A, Read ND, Pallas JA, Loake GJ. (2003) Loss of actin cytoskeletal function and EDS1 activity, in combination, severely compromises non-host resistance in Arabidopsis against wheat powdery mildew. The Plant Journal 34:768–777.[CrossRef][Web of Science][Medline]
Zeidler D, Zahringer U, Gerber I, Dubery I, Hartung T, Bors W, Hutzler P, Durner J. (2004) Innate immunity in Arabidopsis thaliana: lipopolysaccharides activate nitric oxide synthase (NOS) and induce defense genes. Proceedings of the National Academy of Sciences, USA 101:15811–15816.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Kasprowicz, A. Szuba, D. Volkmann, F. Baluska, and P. Wojtaszek Nitric oxide modulates dynamic actin cytoskeleton and vesicle trafficking in a cell type-specific manner in root apices J. Exp. Bot., April 1, 2009; 60(6): 1605 - 1617. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-Q. Wang, A. Feechan, B.-W. Yun, R. Shafiei, A. Hofmann, P. Taylor, P. Xue, F.-Q. Yang, Z.-S. Xie, J. A. Pallas, et al. S-Nitrosylation of AtSABP3 Antagonizes the Expression of Plant Immunity J. Biol. Chem., January 23, 2009; 284(4): 2131 - 2137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. J. Corpas, M. Chaki, A. Fernandez-Ocana, R. Valderrama, J. M. Palma, A. Carreras, J. C. Begara-Morales, M. Airaki, L. A del Rio, and J. B. Barroso Metabolism of Reactive Nitrogen Species in Pea Plants Under Abiotic Stress Conditions Plant Cell Physiol., November 1, 2008; 49(11): 1711 - 1722. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Lee, C. Wie, B. O. Fernandez, M. Feelisch, and E. Vierling Modulation of Nitrosative Stress by S-Nitrosoglutathione Reductase Is Critical for Thermotolerance and Plant Growth in Arabidopsis PLANT CELL, March 1, 2008; 20(3): 786 - 802. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Hong, B.-W. Yun, J.-G. Kang, M. U. Raja, E. Kwon, K. Sorhagen, C. Chu, Y. Wang, and G. J. Loake Nitric oxide function and signalling in plant disease resistance J. Exp. Bot., February 1, 2008; 59(2): 147 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Neill, R. Barros, J. Bright, R. Desikan, J. Hancock, J. Harrison, P. Morris, D. Ribeiro, and I. Wilson Nitric oxide, stomatal closure, and abiotic stress J. Exp. Bot., February 1, 2008; 59(2): 165 - 176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Neill, J. Bright, R. Desikan, J. Hancock, J. Harrison, and I. Wilson Nitric oxide evolution and perception J. Exp. Bot., January 1, 2008; 59(1): 25 - 35. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||