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We have cloned a cDNA, encoding a methyl jasmonate-cleaving enzyme, from tomato cell suspension cultures.. Moreover, when tested in methyl jasmonate- and elicitor-treated cell suspension

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Cloning and expression of a tomato cDNA encoding a methyl

jasmonate cleaving esterase

Christiane Stuhlfelder, Martin J Mueller and Heribert Warzecha

Lehrstuhl fu¨r Pharmazeutische Biologie, Julius-von-Sachs-Institut fu¨r Biowissenschaften, Universita¨t Wu¨rzburg, Germany

Jasmonic acid and its methyl ester are ubiquitous plant

sig-nalling compounds necessary for the regulation of growth

and development, as well as for the response of plants to

environmental stress factors To date, it is not clear whether

methyl jasmonate itself acts as a signal or if its conversion to

jasmonic acid is mandatory prior to the induction of a

def-ense response We have cloned a cDNA, encoding a methyl

jasmonate-cleaving enzyme, from tomato cell suspension

cultures Sequence analysis revealed significant similarity

to plant esterases and to (S)-hydroxynitrile lyases with

an a/b-hydrolase fold structure The coding sequence was

heterologously expressed in Escherichia coli and purified in

a catalytically active form Transcript levels, as well as en-zymatic activity, were determined in different tomato tissues High transcript levels and enzyme activities were found in roots and flowers, while the mRNA level and activity were low in stems and leaves Moreover, when tested in methyl jasmonate- and elicitor-treated cell suspension cultures, transcript levels were found to decrease, indicating that this particular enzyme might be a regulator of jasmonate sig-nalling

Keywords: a/b-hydrolase; cell suspension culture; Lyco-persicon esculentum; methyl jasmonate esterase; Solanaceae

Jasmonic acid (JA) is a ubiquitous plant compound, which

plays a crucial role in the response to wounding or pathogen

attack, as well as in developmental processes, such as fruit

ripening, root growth, and fertility [1] Most of the enzymes

involved in JA biosynthesis have been characterized at a

biochemical and molecular level and the encoding genes

have been cloned Biosynthesis takes place mainly in

chloroplasts and peroxisomes, initiating after the release

of the precursor linolenic acid from membrane stores by

lipases The enzymes lipoxygenase, allene oxide synthase,

and allene oxide cyclase form the biosynthesic intermediate

12-oxo-phytodienoic acid (OPDA) Subsequent action of

OPDA reductase and three cycles of b-oxidation lead to the

formation of JA [2,3] Thereafter, JA may be esterified to its

derivative methyl jasmonate (MeJA) [4], or conjugated with

an amino acid or glucose [5]

For most of the jasmonates it has been shown that they are capable of mediating a response by regulating gene expression [6,7] Analysis of Arabidopsis thaliana mutants impaired in either JA biosynthesis or signalling, gave a deeper insight into the function of single oxylipins [8] The fad3–2fad7–2fad8mutant, which forms almost no trienoic fatty acids [9], is male sterile and fertility could only be restored by application of linolenate or JA Another mutant – opr3 – arrests jasmonate biosynthesis at the OPDA level and is incapable of metabolizing exogenously applied OPDA to JA [10] opr3 mutants displayed a normal defense response towards a variety of pathogens, indicating that OPDA alone is sufficient to initiate an effective defense response However, mutant plants were male sterile and fertility could be restored by the exogenous application of

JA These experiments demonstrate that individual mem-bers of the jasmonate family are involved – at least in Arabidopsis– in different signalling pathways

An Arabidopsis (jar1) mutant with a defect in the jasmonate response has been described The mutant is insensitive to MeJA and does not show root growth inhibition or vegetative storage protein (VSP) induction in response to MeJA [11] Recent analysis of the jar1 locus revealed that its gene product modifies JA via adenylation, which is apparently a prerequisite for downstream signaling The modification requires a free carboxyl group as the enzyme does not accept MeJA as a substrate [12] Therefore, MeJA must be demethylated prior to becoming active Thus, root growth inhibition and VSP expression are mediated by MeJA through JA, indicating that MeJA is not

a mediator on its own in this particular system

On the other hand, OPDA and JA can induce identical genes as well as distinct sets of target genes, suggesting that independent signalling pathways exist [13] and that the combined action of different inducers might be necessary for the full activation of responsive genes [14] However, in

Correspondence to H Warzecha, Lehrstuhl fu¨r Pharmazeutische

Biologie, Julius-von-Sachs-Institut, Julius-von-Sachs-Platz 2,

97082 Wu¨rzburg, Germany.

Fax: + 49 9318886182, Tel.: + 49 9318886162,

E-mail: warzecha@biozentrum.uni-wuerzburg.de

Abbreviations: HNL, (S)-hydroxynitrile lyase; JA, jasmonic acid;

JMT, S-adenosyl- L -methionine jasmonic acid carboxyl

methyltrans-ferase; MeJA, methyl jasmonate; MJE, methyl jasmonate esterase;

MeSA, methyl salicylate; OPDA, 12-oxo-phytodienoic acid; PI,

proteinase inhibitors; PNAE, polyneuridine aldehyde esterase;

RACE, rapid amplification of cDNA ends; VSP, vegetative storage

protein.

Note: The sequence reported herein was deposited under GenBank

accession number AY455313.

Note: A website is available at http://132.187.108.6/

(Received 28 March 2004, revised 19 May 2004,

accepted 25 May 2004)

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the case of MeJA and JA, the biological activities of the

exogenously administered compounds are apparently

iden-tical, possibly because rapid interconversion takes place

in vivo

Another quality of JA-mediated plant defense is the

systemic spread of defense responses after local induction

For instance, in tomato and potato plants the production of

proteinase inhibitors (PI) as an inducible defense response

against feeding Colorado potato beetle is not limited to the

site of their attack, but also appears in distant leaves of the

plant [15] The herbivore attack induces JA biosynthesis

locally via systemin, an 18 amino acid signal peptide

However, the induction of PI genes could be found also in

distant parts of the plant, which requires a long distance

signalling component Grafting experiments with tomato

mutants deficient in either JA biosynthesis or JA perception

proved that a jasmonate, rather than systemin, is the signal

which is translocated through the plant [16] Rootstocks of

the spr-2 mutant, which are impaired in JA biosynthesis,

were not capable of generating a transmissible signal that

could induce PI expression in wild-type scions, while

wounded wild-type root stocks did induce PI expression

in spr-2 scions

A strong candidate for a transmissible jasmonate signal is

the JA-conjugate, MeJA The volatile ester can diffuse

through membranes and can be found in the headspace

above wounded leaves [17], suggesting that MeJA might be

an interplant communication signal [18] Moreover, it has

been speculated that the physical role of MeJA is to

mobilize JA [19] The proof of this hypothesis might come

from a more detailed understanding of how plants form

MeJA from JA, and vice versa A recent study identified an

S-adenosyl-L-methionine:jasmonic acid carboxyl

methyl-transferase (JMT) from Arabidopsis, which converts JA to

MeJA [4] Constitutive overexpression of JMT tripled the

MeJA content of transgenic plants and also induced

JA-responsive genes Therefore, transgenic plants with elevated

JMT levels showed enhanced resistance against the

necro-trophic fungus Botrytis cinerea, suggesting a prominent role

for the enzyme in jasmonate-mediated defense

It is not yet clear whether MeJA functions as a paracrine

signal that is released from sites of pathogen attack to

induce defense genes at distant sites Moreover, it remains to

be clarified whether MeJA is a mediator on its own that

elicits JA responses without prior hydrolysis to JA

How-ever, if MeJA is considered to be a signal, there must be a

way to regulate the signal by controlled formation and –

perhaps more importantly – by its controlled inactivation

A candidate for performing the latter task is an esterase,

previously characterized in tomato [20] Enzyme activity has

been found to be constitutively present in cell cultures of

many taxonomically distant plant species In tomato cell

cultures, only one MeJA-hydrolysing enzyme could be

identified by activity-guided protein purification The

tomato esterase has been purified and characterized from

tomato cell suspension cultures Owing to its MeJA-cleaving

activity, we named the enzyme methyl jasmonate esterase

(MJE) Yet, it remains to be established whether MJE has a

function in JA/MeJA signalling As a first step to investigate

this, we cloned a cDNA from tomato encoding MJE

Analysis of transcript incidence showed that MJE is

differently expressed in different organs as well as after

elicitation, indicating that this enzyme might be involved in jasmonate signalling

Experimental procedures

Plant material Tomato plants (Lycopersicon esculentum cv Moneymaker) were grown in the greenhouse under conditions of 16 h light and 8 h darkness The growth temperature range was 16–22C with a relative humidity of 60–70%

Cell suspension cultures (L esculentum) were grown in

1 L Erlenmeyer flasks in Linsmaier & Skoog media [21] for

7 days under continuous light (600 lux) on orbital shakers (100 r.p.m.) at 24 ± 2C Cells were harvested by suction filtration, shock frozen in liquid nitrogen, and stored at )80 C until use

Nucleic acid isolation and blot analyses Plant material for the isolation of nucleic acid was either 4-day-old cell suspension culture or 8-week-old plants Total RNA from suspension cultures was isolated either accord-ing to the protocol described previously [22], or with the TRIzol reagent (Invitrogen), and used for RT-PCR or Northern blots, respectively Isolation of RNA from plant material was carried out using the RNeasy Plant Mini Kit (Qiagen) For DNA purification the protocol described previously [23] was employed

Standard protocols were used for the transfer of RNA and DNA after electrophoretic separation [24] Hybridiza-tion of RNA or DNA transferred to nylon membranes was performed using a nonradioactive digoxigenin-probe label-ling system (Roche)

RT-PCR and cloning of partial- and full-length cDNA Two degenerated primers were designed according to previously determined peptides Sequences were YTTRTC RCANACNACRTANACNCKRTGNACNSWNCCRTA for MJErev4 and GAYATGGCNGCNWSNGGNATH AAYCC for MJEfor3.1 With total RNA from cell suspen-sion cultures and primer MJErev4 for first-strand synthesis, cDNA was produced using the RT-PCR system from Qiagen RT-PCR conditions were 30 min at 50C, 15 min at 95 C; five cycles of 30 s at 94C, 1 min at 40 C and 1 min at

72C, followed by 30 cycles of 30 s at 94 C, 1 min at 45 C and 1 min at 72C Gel electrophoresis, DNA elution and modification was carried out according to standard protocols [24] After cloning of the PCR product into the vector

pGEM-T (Promega) and sequencing (automated sequencer LI-COR 4200), two homologous primers were designed for the rapid amplification of cDNA ends (RACE) (RACEfor: GTGA CAGCTTTCATGCCTGG; and RACErev: ATCCTGT CCGTTGTTGTAAAC) 5¢- and 3¢-RACE was performed using the SMART II system (BD Bioscience) Full-length cDNA for expression was cloned by another RT-PCR with primers fullMJEforMQ (GCATGCAGGGTGATAAAAA TCACTTTGTA) and fullMJErev (AAGGATCCATAA TATTTTTGCGAAATC), adding restriction sites for SphI and BamHI, respectively The PCR product was cloned into vector pDRIVE (Qiagen), sequenced and subcloned into

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expression vector pQE70 (Qiagen) via SphI and BglII

restriction sites

Overexpression and purification

Escherichia coliM15 cells harbouring the MJE expression

plasmid were cultured at 20C on a rotary shaker

(200 r.p.m.) Twenty-four hours after induction with

1 mMisopropyl thio-b-D-galactoside, cells of a 5 L

suspen-sion were harvested and lysed by sonication The crude

extract was cleared by centrifugation (10 000 g) and

separ-ated on Q-Sepharose fast-flow 26/20, gel-filtration on

Sephacryl S-100 HR 26/60, and MonoQ HR 5/5 (all

Amersham Biosciences), according to a procedure described

previously [20] For metal affinity chromatography, Talon

resin (BD Bioscience) was utilized Analysis of proteins was

performed with SDS/PAGE (12.5%) under denaturating

conditions, and gels were silver stained as described

previously [25] For Western blot analysis, proteins were

blotted onto nitrocellulose filters and detected with

anti-6·His primary antibody, alkaline phosphatase-labeled

secondary antibody and chemoluminescent substrate

(CDP-Star; Roche)

MJE activity was monitored according to a previously

published protocol [20]

Results

Isolation of MJE cDNA

We previously described an MJE, which is the only or at

least the predominant protein with MJE activity identified in

tomato cell cultures On the basis of the partial amino acid

sequences obtained from the purified MJE [20], two

degenerate primers were developed This method has been

proven successful in several reports [26,27] and should lead

to the identification of the encoding gene rather than

orthologous genes Owing to the similarity of the peptide

fragments with sequences of known proteins, the sequence

PF18b (DMAASGINPK) was utilized to design a sense

primer, and sequence PF23 (RVYVVCDKD) was used for

the generation of an antisense primer Using tomato cDNA

as a template, a 498 bp fragment was amplified by PCR

Sequencing revealed a DNA stretch that encodes a peptide

with sequence similarity to a/b-hydrolase fold proteins (data

not shown), some of which have been previously aligned to

the internal fragments of purified MJE [20] To obtain the

full-length cDNA by RACE, two sequence-specific primers

were synthesized, generating overlapping fragments after

5¢- and 3¢-RACE, respectively Sequencing and annealing of

the 5¢ and the 3¢ sequence revealed an ORF of 789 bp,

encoding a 262 amino acid protein (Fig 1) All four peptides

from the purified tomato protein could be identified in the

deduced amino acid sequence, which substantiates that the

cloned cDNA encodes the purified protein The calculated

molecular mass of the encoded protein is 29 524.93 Da and

the pI¼ 5.52 The calculated mass of the encoded protein

corresponds well with the molecular mass of  28 000

determined by SDS/PAGE for the purified plant protein

Comparison of the N-termini showed that the protein

originally purified from tomato lacked two amino acids:

Met and Glu It could not be concluded if this was a result of

degradation of the protein during the purification process or whether the protein was modified in vivo No peptide signal for subcellular targeting could be identified

Sequence alignment Sequence analysis and alignment with known proteins from GenBank showed a high similarity of MJE to ethylene-induced esterase from Citrus sinensis (47% identity, 65% positivity) [28], the tobacco salicylic acid binding protein 2 (SABP2) (47% identity, 65% positivity) [29], the polyneu-ridine aldehyde esterase (PNAE) from Rauvolfia serpentina (44% identity, 65% positivity) [27], and several lyases involved in the biosynthesis of cyanogenic compounds in different plant species [36% identity to (S)-hydroxynitrile lyase (HNL) from Hevea brasiliensis [30], 33% to

(S)-Fig 1 Tomato methyl jasmonate esterase cDNA and deduced protein sequence Peptides determined by sequencing of the purified protein are boxed and the names of the peptides are indicated in italic letters above Nucleic acids of the ORF are shown in capital letters, while 5¢ and 3¢ untranslated regions are in lower case letters The putative amino acid residues of the catalytical triad of a/b-hydrolase fold pro-teins are marked with an asterisk.

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acetone-cyanohydrin lyase from Manihot esculentum] [31].

In addition, several putative proteins from the Arabidopsis

genome exhibited high sequence similarity to MJE For

sequence alignment and analysis, only known or at least

partially characterized proteins were included (Fig 2) As

all the aligned proteins belong to the extremely divergent

family of a/b-hydrolase fold proteins, it could be assumed

that MJE is a member of this protein family As further

support of this assumption, MJE shows the highly

con-served amino acid residues forming the catalytic triad [32] –

nucleophile, acid, and a histidine – represented by serine at

position 83, aspartic acid at position 211, and histidine at

position 240 (Fig 2) Moreover, it has been shown that

MJE could be irreversibly inhibited by

phenylmethanesulfo-nyl fluoride [20], a specific inhibitor of serine hydrolases [33]

Bacterial expression and purification of tomato MJE

To obtain unequivocal evidence of the identity of the cloned

sequence, MJE cDNA was subcloned into a bacterial vector

for heterologous expression As amplification of the coding

sequence with a forward primer homologous to the 5¢-end failed, the primer sequence had to be modified for enhanced binding and amplification Primer design was carried out using the Vector NTI Software (Informax) Thereby, a modified N-terminus of the encoded protein was created in which Glu and Lys in positions 2 and 3, respectively, were replaced with a single Gln

At the C-terminus a 6·His extension was added to simplify subsequent purification of the protein Crude extracts of E coli M15 cells harbouring the pQE-MJE plasmid showed MJE-esterase activity (1.64 pkatÆmg)1) after isopropyl thio-b-D-galactoside induction, while wild-type M15 cells did not show any MJE activity This value was comparable with the activity found in crude extracts from tomato cell suspension culture in previous experiments (1.77 pkatÆmg)1) [20], but was much less than expected for

an enzyme from heterologous bacterial expression of the cDNA For visualization of proteins, bacterial extracts were subjected to SDS/PAGE In a comparison of MJE-produ-cing E coli with wild-type cells, no prominent protein with the approximate size of MJE (29 kDa) could be detected

Fig 2 Multiple sequence alignment Alignment of methyl jasmonate esterase (MJE) with a/b-hydrolase fold proteins from different plant species EIE, ethylene-induced esterase from Citrus sinensis (GenBank accession number AAK58599); SABP2, salicylic acid-binding protein from Nic-otiana tabacum (AY485932); PNAE, polyneuridine aldehyde esterase from Rauvolfia serpentina (AAF22288); Pir7b, defense-related rice gene from Oryza sativa (CAA84024); HNL, (S)-hydroxynitrile lyase from Hevea brasiliensis (P52704).

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after Coomassie Blue staining (data not shown) This

observation suggests that MJE is not abundantly produced

or that it is not stable in E coli Because of the low

abundance in E coli, a four-step purification protocol was

employed to purify the enzyme (Table 1) Catalytically

active enzyme was obtained after anion exchange on

Q-Sepharose, gel filtration with Sephacryl S-100, further

anion-exchange chromatography on MonoQ, and finally

separation on immobilized metal affinity chromatography

(Talon resin) Starting from a 5 L bacterial suspension

culture, MJE(His)6could be enriched 203-fold, resulting in

52 lg of protein Figure 3A shows the silver-stained

poly-acrylamide gel from the purified fraction Although some

impurities are visible, we assume that solely the MJE is

responsible for MeJA-cleaving activity, as wild-type E coli

is not capable of cleaving MeJA An antibody specific for

hexa-histidine epitopes was used in an immunoblot

experi-ment to confirm the presence and the size of the

recombin-ant protein As shown in Fig 3B, extracts from E coli

harbouring pQE-MJE showed a band of 29 kDa

repre-senting MJE(His)6, while wild-type bacteria did not

Southern blot analysis

For Southern blot analysis, genomic DNA from cell

suspension cultures or greenhouse-grown tomato plants

(L esculentum cv Moneymaker) was digested with BamHI,

EcoRI, or HindIII restriction enzymes and probed with a

full-length cDNA of MJE at high stringency It should be

noted that the MJE-coding sequence has a recognition site

for EcoRI at position 204 and therefore should show at least two bands in a Southern blot analysis In addition to this, the probe hybridized with multiple bands (Fig 4)

In the case of HNL from Cassava – which shows high similarity to MJE – several gene copies were reported [34] It could not be concluded from our data whether tomato contains several homologous genes, if some signals are a result of probe hybridization with pseudogenes, or if multiple bands occur owing to the presence of recognition sites for the utilized restriction enzymes within introns (as assumed for the HNL from Hevea) [30] However, during the purification of MJE there was no evidence for the expression of isoenzymes, although, if present, they might have different catalytic properties

Northern blot analysis and induction of MJE expression

in cell cultures Northern blot analysis was used to determine MJE transcript levels in different plant organs Therefore, total RNA from roots, leaves, stems, and flowers was probed with full-length MJE cDNA Transcripts of 1 kb were present in all plant tissues and significant variations in their amounts could be detected (Fig 5A) High levels of MJE mRNA could be found in roots and flowers, while low-to-moderate amounts were present in the leaves and stems of tomato plants The RNA levels correspond well with the MJE activity found in different plant organs, showing that high enzymatic activity correlates with a high transcript level (Fig 5B)

Table 1 Purification of recombinant methyl jasmonate esterase.

Purification step

Total protein (mg)

Total activity (pkat)

Specific activity (pkat)

Purification (fold)

Recovery (%)

Fig 3 SDS/PAGE and Western blot analysis

of methyl jasmonate esterase (MJE) purified from recombinant bacteria (A) Silver-stained proteins after separation by SDS/PAGE (12.5% gel) M, marker proteins (sizes are indicated on the left); lane 1, purified fraction after the last purification step MJE is indica-ted by an arrow (B) Western blot of crude bacterial extracts after transfer to nitrocellu-lose An antibody specific for 6·His modified proteins was used Lane M, protein standard; lane 1, Escherichia coli harbouring expression plasmid pQE70-MJE; lane 2, E coli without the expression plasmid MJE is indicated with the arrow.

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In order to evaluate whether transcript levels could be

regulated by external stimuli, cell suspension cultures were

treated with MeJA, methyl salicylate (MeSA), or chitosan,

and mRNA levels were determined in a time-dependent

manner While basal levels of mRNA were high in untreated

cultures, the levels decreased 1 h after MeJA treatment and

returned to basal levels 8 h postinduction (Fig 5C) A

similar time course could be observed after treatment with

the elicitor chitosan, although with a slightly delayed

response No changes in mRNA levels were observed after

treatment with MeSA

Discussion

Sequence alignment of the MJE revealed high similarity to

a/b-hydrolase fold proteins of different origin and with

diverse properties Notably, all plant proteins of known

function with high sequence similarity to MJE appear to be

involved in the defense response and/or secondary

metabo-lism Among the related proteins is the ethylene-induced

esterase from C sinensis [28], a recently discovered SABP2

from tobacco [29], the Pir7b protein from Oryza sativa,

hydroxynitrile lyases of different origins and the PNAE

from the medicinal plant R serpentina Nevertheless, the

substrate acceptance and enzymatic activity of those

enzymes, if known, is highly diverse With the increasing

number of specified plant enzymes of this group of the

a/b-hydrolase family, it might be assumed that they have arisen

from a common ancestral gene and the descendants

partially occupied species-specific niches in secondary

metabolism Similar scenarios have been described for plant

O-methyl transferases [35,36] or dioxygenases [37] It should

Fig 4 Southern blot analysis of total genomic DNA from tomato

plants Fifty micrograms of DNA was digested overnight with

restriction enzymes and separated on a 1% agarose gel M, size

standard; lane 1, BamHI-digested DNA; lane 2, EcoRI digest; lane 3,

HindIII digest.

Fig 5 Levels of methyl jasmonate esterase (MJE) transcripts in dif-ferent tissues and after induction (A) Northern blot of total RNA from different tissues hybridized with the full-length cDNA probe RNA was isolated from roots, leafs, stems and flowers The lower panel shows 17S rRNA as a loading control (after methylene-blue staining); the results shown were consistent in three different experiments (B) Specific activity of MJE in different plant organs (C) Time course

of MJE transcript abundance after treatment with methyl jasmonate (MeJA), methyl salicylate (MeSA), and chitosan Loading controls show the ethidium bromide-stained gel prior to transfer.

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be noted that in the Arabidopsis genome at least 20 genes

with homologies to HNL and PNAE could be found It is

unlikely that they have similar properties to the

a/b-hydrolase fold proteins mentioned above, as they occur only

in distinct plant families or even species and their substrates

are not present in Arabidopsis On the other hand, MJE

activity could be found in several plant systems From the 18

plant cell suspension cultures of taxonomically distant

species tested to date, virtually all exhibited MJE activity

[20] One might speculate that the MJEs of different species

are encoded by orthologous genes

Whenever analysed, plant cells and tissues contain JA

and its methyl ester, MeJA, side by side In most reports,

authors have made little effort to distinguish between the

biological activity of the two compounds and usually only

JA content is measured If values of both JA and MeJA are

published, the ratios depend on the plant species and the

tissue analysed and vary from 3 : 2 (JA/MeJA) in

Arabid-opsisleaves [4] to about 10 : 1 in tomato flowers [38] For

tomato cell suspension cultures, a JA/MeJA ratio of almost

1 : 1 was found [39] To date there is no way of

distinguishing between the function of the two compounds

on a physiological basis as they can be rapidly converted

from one into the other For the Arabidopsis jar1 mutant, it

has been shown that the role of JAR1 is to modify JA via

adenylation of the carboxyl group [12] As MeJA is not

accepted as a substrate in this putative essential step

involved in JA signalling, it is probable that MeJA has to

be hydrolyzed by MJE in order to become metabolically

activated In this case, MeJA might represent a pool of inert

JA conjugates or plays a role as signalling molecule between

individual cells [19] The inverse activity of JMT and MJE

suggests that both enzymes should be spatially separated

MJE transcript levels were analyzed by Northern

hybrid-ization and revealed a high, constitutive expression in roots

and flowers and low RNA levels in leaves and stems,

suggesting that enzyme activity could be found in all tissues

These data were supported by activity assays of MJE in

different plant organs, which signify that high enzymatic

activity is contingent on high transcript levels

Interestingly, undifferentiated tomato cell suspension

cultures accumulate both JA and MeJA at almost equal

levels while displaying high MJE activity, suggesting that

individual cells may contain both JMT and MJE activity

However, it is unlikely that a cell forms MeJA under the

expenditure of energy and degrades it immediately

Intra-cellular separation of MeJA synthesis and hydrolysis would

be one way to avoid a treadmill situation, yet analysis of

tomato MJE and Arabidopsis JMT reveals no evidence for

subcellular targeting of the enzymes and, thus, both

enzymes should reside in the cytosol Alternatively,

sub-strates may be presented for the enzymes in a highly

regulated manner

To this end, it would be an appealing scenario that a cell

could distinguish between endogenously formed and

exo-genous MeJA Endoexo-genously formed MeJA might be

exported and not hydrolysed, while MeJA coming from

outside the cell may be recognized as an alarm signal that –

after hydrolysis to JA – functions as intracellular defense

signal In fact, a similar situation occurs in mammals

Stimulated neutrophils may synthesize (within minutes)

leukotrienes, which are exported into the extracellular

environment where they act as autocrine and paracrine signals However, neutrophils are also capable of taking up leukotrienes for intracellular catabolism, thereby locally restricting and terminating the signal

Transcript levels were also monitored after stimulation

of tomato cell cultures with exogenous MeJA or the elicitor chitosan, which induces intracellular synthesis of jasmonates in tomato [40] Constitutively high MJE accumulation transiently declined within 2 and 3 h after the treatments, respectively Decreasing transcript levels may not immediately affect enzyme activity and thus exogenous MeJA can still be hydrolysed to JA for some time However, downregulation of MJE by exogenous MeJA may limit MeJA hydrolysis and JA signalling when cells are exposed to elicitors/jasmonates over longer time-periods Interestingly, basal transcript levels of JMT in Arabidopsisleaves are low, and stimulation by exogenous MeJA transiently increases JMT formation Overexpres-sion of JMT cDNA has been shown to increase the synthesis of MeJA [4], which, in turn, may leave producer cells and function as an intercellular signal As MJE activity has been detected in all plant tissues examined so far, MJE-harbouring cells may trap the volatile and highly diffusible MeJA entering cells from the outside by hydrolysis to JA anions inside the cells Increasing JA levels might then elicit specific responses In the future, generation and careful analysis of transgenic plants that either constantly accumulate MJE or that are devoid of MJE will help to solve the question of whether or not MeJA is a paracrine or even a long-distance signal

Acknowledgements

This work was supported by the Sonderforschungsbereich (SFB) 567 The authors thank Susanne Michel for performing DNA sequencing.

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