Search tips
Search criteria 


Logo of f1000bioLatest ContentReportsReportsReports
F1000 Biol Rep. 2010; 2: 15.
Published online 2010 February 24. doi:  10.3410/B2-15
PMCID: PMC2948352

Abscisic acid (ABA) receptors: light at the end of the tunnel


The plant hormone abscisic acid (ABA) plays a role in several aspects of plant growth and development. Understanding how this hormonal stimulus is sensed and transduced turned out to be one of the major tasks in the field of plant signaling. A series of recent papers proposed several different proteins that could receive the ABA signal and initiate the signaling cascade. The winner appears to be PYR/PYL/RCAR (PYrabactin Resistance/PYrabactin Resistance-Like/Regulatory Component of Abscisic acid Receptor) proteins, as crystal structures were recently published. The crystal structures support the idea that upon ABA binding to a PYR/PYL/RCAR protein, the activity of a phosphatase 2C, with known repressive activity on ABA signaling, is inhibited.

Introduction and context

The first report of this series of disparate communications about abscisic acid (ABA) receptors began when Razem et al. [1] claimed that the RNA-binding protein FCA, known to promote flowering, was an ABA receptor. They performed binding experiments using recombinant FCA protein purified from Escherichia coli and radiolabeled (+) ABA. The FCA story ended quickly when the Macknight and Day group reported that FCA did not bind ABA [2], leading the authors, Razem et al., to retract their paper [3].

The second protein proposed as an ABA receptor was CHLH (magnesium-chelatase subunit H), an Arabidopsis homolog of a bean ABA-binding protein [4]. These authors showed that Arabidopsis CHLH was able to bind ABA and that RNAi (RNA interference) lines with reduced expression of CHLH were insensitive to ABA. However, given the strength of the chlh mutant, chlh alleles should have been isolated as ABA-insensitive mutants in previous genetic screens but were not. Furthermore, the barley magnesium-chelatase XanF did not bind ABA and none of the different XanF mutants showed any altered ABA responses [5]. Nonetheless, it is possible, despite the high amino acid identity of the Arabidopsis and barley CHLH proteins (close to 82%), that only the Arabidopsis CHLH would function as an ABA receptor.

The third protein proposed as an ABA receptor was GCR2, a hypothetical G protein-coupled receptor (GCR) with the expected seven-transmembrane (7TM) domain structure [6]. Liu et al. [6] claimed that recombinant GCR2 protein (also prepared in E. coli) bound ABA. But other groups showed that GCR2 was not necessary for several ABA responses [7,8] and that it was more similar to bacterial lanthione synthetases [9,10] than to a 7TM protein, as Liu et al. [6,10] stated. The main problem of Liu et al. was that they used FCA as a positive control in their binding assays, predictably leading the Macknight and Day group to show that GCR2 did not bind ABA either [11]. All of these issues are still under dispute because, despite several studies that failed to confirm the results, there was no formal retraction by Liu et al. [6] or any new findings to support GCR2 as a bona fide ABA receptor.

Major recent advances

In 2009, two new groups of proteins attempted to gain membership in the ABA receptor club. The first group is comprised of two membrane proteins (GTG1 and GTG2) with nine predicted transmembrane domains [12]. GTG1 and GTG2 both bind ABA, and gtg1;gtg2 mutant plants showed reduced but not completely abolished ABA responses. The in vitro binding assays with GTG1 and GTG2 were performed by expressing them in E. coli and using the soluble fraction. The stoichiometry of the binding was very low, such that only 1% of the GTGs purified from E. coli were able to bind ABA (Table 1). The authors attributed this insignificant binding to poor protein purification, solubilization, or renaturation. However, as they admitted, physiological environments more representative of those experienced by eukaryotic membrane proteins will be needed to demonstrate that GTG1 and GTG2 are true ABA receptors.

Table 1.
Biochemical characteristics of the proposed abscisic acid

HABI1, ABI1, and ABI2 encode protein phosphatase 2 Cs (PP2Cs) that act as negative regulators of ABA signaling [13]. The second group of candidate ABA receptors is comprised of proteins (pyrabactin resistance/pyrabactin resistance-like/regulatory component of abscisic acid receptor, or PYR/PYL/RCAR) that, through ABA binding, would inhibit the known repressive activity of PP2Cs on ABA signaling. Park et al. [14] used an elegant chemical genetic strategy to identify and characterize a family of StAR-related lipid transfer (START) proteins (called PYR1/PYL1-13). They used heteronuclear single-quantum coherence-nuclear magnetic resonance to show that, in the presence of saturating amounts of bioactive ABA, PYR1 binds HAB1 (homology to ABA-insensitive 1 [ABI1]). The quadruple mutant pyr1;pyl1;pyl2;pyl4 displayed ABA insensitivity in seed germination and root growth assays [14] and in ABA-regulated stomatal movements [15]. Park et al. [14] used recombinant proteins to demonstrate that PYR1 inhibits the phosphatase activity of a PP2C only in the presence of ABA. Another group used a yeast two-hybrid approach for HAB1-interacting proteins and isolated three proteins from this family (PYL5, PYL6, and PYL8) [16]. Ma et al. [17] also used a yeast two-hybrid approach for binding partners for ABI2 and identified a START protein (which they named RCAR1). They used isothermal calorimetric analysis to demonstrate that (S)-ABA binds to RCAR1 and ABI2. Park et al. [14] suggested that the PYR/PYL/RCAR interactions with PP2Cs are sensitive to protein concentration, implying that (at least in yeast) some of the PYR/PYL/RCARs can interact with PP2Cs in the absence of ABA. However, inhibiting the phosphatase activity of ABI1/2 with RCAR1/PYL9 requires ABA because when Ma et al. [17] added greater than 15-fold excess RCAR1/PYL9 to 0.1 mg of ABI1/2, there was no inhibition of the phosphatase activity in the absence of ABA.

Crystal structures of PYR1, PYL1, and PYL2 were recently published [18-22]. In the ligand-free conformation, the receptors expose a pocket that is vacant and that is exclusively occupied later by ABA. Two highly conserved surface loops are located at the pocket entrance. When ABA binds, allosteric changes in the two loops close the pocket, confining ABA inside the pocket and thereby exposing a PP2C domain-binding site on the loops. PP2C binding stabilizes the closed stage, thereby reducing ABA dissociation. This explains why the affinity of ABA for PYR/PYL/RCARs is increased by more than 10-fold in the presence of PP2Cs. All of the structures show that when ABA binds to PYR/PYL/RCAR, they inhibit the phosphatase activity of PP2C, resulting in full activation of the ABA signaling pathway. Because the PP2C-binding site perfectly coincides with the PP2C active site, the ABA-bound PYR/PYL/RCAR receptors can be considered competitive inhibitors of the PP2C substrates. Melcher et al. [18] elegantly supported this hypothesis by showing that increasing concentrations of a PP2C substrate (a SnRK2.6 peptide containing residues 170-180 and a phosphorylated serine at position 175) de-repressed the inhibition of the PP2C activity caused by ABA-bound PYL2.

Future directions

The structures definitely show that PTR/PYL/RCAR proteins are bona fide ABA receptors. But what about the other proposed ABA receptors? Is there still room in the ABA signaling pathway for them? To convince the scientific community that their genes are ‘bona fide ABA receptors’, these researchers should first demonstrate in a more careful way that their putative receptors truly bind ABA. Given that GCR2, GTGs, and CHLH are membrane proteins, it would be more appropriate to perform ABA-binding assays in a membranous environment, perhaps in a heterologous eukaryotic system that does not have an ABA signaling pathway. Showing that ethylene bound to yeast expressing ETR1 (ethylene receptor 1) [23] and the assays demonstrating that auxin bound to TIRs (transport inhibitor responses) in insect [24] and Xenopus [25] cells are examples that should be imitated.

In general, we expect that mutants in presumed receptors should show reproducible biological effects for at least some final hormonal responses. This expectation was met with the mutants in CHLH, GCR2, GTG, and PYR/PYL/RCAR in Arabidopsis, which showed phenotypes affecting seed germination, lateral root formation, or stomatal responses. On the other hand, fca-1 mutants had no defects in any typical ABA responses. There is still some dispute about whether GCR2 and CHLH truly bind ABA, but because of the mutant phenotypes, these proteins may act as modulators or transducers of ABA signaling rather than as receptors. It will be a challenge to envision how membrane proteins such as GCR2 and GTGs could interact with the PYR/PYL/RCAR receptors in order to regulate the binding of ABA or modulate its signaling.

Interestingly, structural studies on the auxin [26] and gibberellin (GA) [27] receptors also proposed that hormones stabilize the interactions between their respective receptors and downstream repressors, even though the types of molecules involved in all of these different hormonal signaling pathways are entirely different. The ABA receptors directly bind ABA, and this is therefore analogous to the GA receptor system, as GA binds directly to its receptor, GA insensitive dwarf 1 (GID1), and ABA binding and GA binding to their receptors both produce allosteric modifications necessary for the interaction with their effectors, PP2Cs and DELLAs, respectively. However, there are distinct mechanistic details; while DELLA binding to GID1 induces a conformational change in the GRAS domain of DELLA proteins, thus facilitating binding to the F-box protein SLY1 that targets the DELLA proteins for degradation, the binding of PP2C directly inhibits the phosphatase activity because the active site of PP2C is also the site that binds to the ABA receptor.

Gene redundancy explains why ABA loss-of-function mutants for single PYR/PYL/RCAR genes were not obtained as Park et al. [14] had to build triple or quadruple pyr/pyl/rcar mutants to show strong ABA insensitivity. It will be interesting to investigate whether all members of this protein family are redundant or whether any have unique functions or show cell-specific expression patterns. Why were gain-of-function pyr/pyl/rcar mutants (i.e., those that would constitutively inhibit PP2C activity, even in the absence of ABA) not isolated? As two loops are in charge of exposing the PP2C-binding site, perhaps mutation at more than one amino acid residue would be necessary to permanently close the lids and recruit PP2C to its inhibitory stage. However, hypermorphic ABA-insensitive mutants have been obtained [28,29]. When a conserved glycine in the active sites of ABI1 (G180), ABI2 (G168), and HAB1 (G246) was mutated to Asp, dominant ABA-insensitive phenotypes were obtained, presumably because the interaction of the mutated PP2Cs with PYR1 was disrupted, thereby eluding the negative regulation of the ABA-PYR/PYL/RCAR complex. However, these mutants also showed reduced phosphatase activity, at least when using heterologous substrates. To add another perspective to the inhibitory role for PP2C, it was recently shown [29] that ABI1G180D was more efficiently sent to the nucleus than was wild-type ABI1, suggesting that the hypermorphic phenotype is at least partly mediated by nuclear localization, despite the reduced dephosphorylating activity of ABI1G180D.

Although historically it used to be thought that plant hormone receptors must be plasma membrane proteins with expected domains for canonical receptors, the receptors for auxin, jasmonic acid, GAs, and now PYR/PYL/RCAR for ABA show that open minds can lead to new discoveries. Nonetheless, in order for the scientific community to accept and adopt such new discoveries, multiple approaches are needed.


We apologize to all researchers whose work we could not mention due to space constraints. JM is supported by the National Research Council of Argentina (CONICET) and Universidad de Buenos Aires and by grants ANPCyT-PICT2005/PICT2007 and UBACyT-X155. SM is supported by the United States Department of Agriculture Current Research Information System (5335-21000-030-00D).


abscisic acid
abscisic acid-insensitive protein phosphatase mutant
magnesium-chelatase subunit H
flowering time control protein
G protein-coupled receptor
gibberellin insensitive dwarf 1
homology to abscisic acid-insensitive 1
protein phosphatase 2C
pyrabactin resistance-like
pyrabactin resistance
regulatory component of abscisic acid receptor
steroidogenic acute regulatory protein (StAR)-related lipid transfer.


The electronic version of this article is the complete one and can be found at:


Competing interests

The authors declare that they have no competing interests.


1. Razem FA, El-Kereamy A, Abrams SR, Hill RD. The RNA-binding protein FCA is an abscisic acid receptor. Nature. 2006;439:290–4. doi: 10.1038/nature04373. [PubMed] [Cross Ref]
2. Risk JM, Macknight RC, Day CL. FCA does not bind abscisic acid. Nature. 2008;456:E5–6. doi: 10.1038/nature07646. [PubMed] [Cross Ref]
3. Razem FA, El-Kereamy A, Abrams SR, Hill RD. Retraction. The RNA-binding protein FCA is an abscisic acid receptor. Nature. 2008;456:824. doi: 10.1038/nature07645. [PubMed] [Cross Ref]
4. Shen YY, Wang XF, Wu FQ, Du SY, Cao Z, Shang Y, Wang XL, Peng CC, Yu XC, Zhu SY, Fan RC, Xu YH, Zhang DP. The Mg-chelatase H subunit is an abscisic acid receptor. Nature. 2006;443:823–6. doi: 10.1038/nature05176. [PubMed] [Cross Ref] f1000 Factor 8.0 Exceptional
Evaluated by Martin Robert McAinsh 31 Oct 2006, Seth J Davis 27 Nov 2006
5. Muller AH, Hansson M. The barley magnesium chelatase 150-kd subunit is not an abscisic acid receptor. Plant Physiol. 2009;150:157–66. doi: 10.1104/pp.109.135277. [PubMed] [Cross Ref]
6. Liu X, Yue Y, Li B, Nie Y, Li W, Wu WH, Ma L. A G protein-coupled receptor is a plasma membrane receptor for the plant hormone abscisic acid. Science. 2007;315:1712–6. doi: 10.1126/science.1135882. [PubMed] [Cross Ref] f1000 Factor 10.2 Exceptional
Evaluated by Seth J Davis 13 Mar 2007, Emmanuel Liscum 22 Mar 2007, Elena Alvarez-Buylla 26 Mar 2007, Martin Robert McAinsh 27 Mar 2007, Caren Chang 29 May 2007
7. Guo J, Zeng Q, Emami M, Ellis BE, Chen JG. The GCR2 gene family is not required for ABA control of seed germination and early seedling development in Arabidopsis. PLoS One. 2008;3:e2982. doi: 10.1371/journal.pone.0002982. [PMC free article] [PubMed] [Cross Ref]
8. Gao Y, Zeng Q, Guo J, Cheng J, Ellis BE, Chen JG. Genetic characterization reveals no role for the reported ABA receptor, GCR2, in ABA control of seed germination and early seedling development in Arabidopsis. Plant J. 2007;52:1001–13. [PubMed] f1000 Factor 6.0 Must Read
Evaluated by Sheila McCormick 13 Nov 2007
9. Chen JG, Ellis BE. GCR2 is a new member of the eukaryotic lanthionine synthetase component C-like protein family. Plant Signal Behav. 2008;3:307–10. [PMC free article] [PubMed]
10. Johnston CA, Temple BR, Chen JG, Gao Y, Moriyama EN, Jones AM, Siderovski DP, Willard FS. Comment on ‘A G protein coupled receptor is a plasma membrane receptor for the plant hormone abscisic acid’ Science. 2007;318:914. doi: 10.1126/science.1143230. author reply 914. [PubMed] [Cross Ref]
11. Risk JM, Day CL, Macknight RC. Reevaluation of abscisic acid-binding assays shows that G-Protein-Coupled Receptor2 does not bind abscisic Acid. Plant Physiol. 2009;150:6–11. doi: 10.1104/pp.109.135749. [PubMed] [Cross Ref] f1000 Factor 3.0 Recommended
Evaluated by Michael Blatt 19 May 2009
12. Pandey S, Nelson DC, Assmann SM. Two novel GPCR-type G proteins are abscisic acid receptors in Arabidopsis. Cell. 2009;136:136–48. doi: 10.1016/j.cell.2008.12.026. [PubMed] [Cross Ref] f1000 Factor 6.4 Must Read
Evaluated by Nathan Nelson 15 Jan 2009, Andrew Tobin 12 Feb 2009
13. Hirayama T, Shinozaki K. Perception and transduction of abscisic acid signals: keys to the function of the versatile plant hormone ABA. Trends Plant Sci. 2007;12:343–51. doi: 10.1016/j.tplants.2007.06.013. [PubMed] [Cross Ref]
14. Park SY, Fung P, Nishimura N, Jensen DR, Fujii H, Zhao Y, Lumba S, Santiago J, Rodrigues A, Chow TF, Alfred SE, Bonetta D, Finkelstein R, Provart NJ, Desveaux D, Rodriguez PL, McCourt P, Zhu JK, Schroeder JI, Volkman BF, Cutler SR. Abscisic acid inhibits type 2C protein phosphatases via the PYR/PYL family of START proteins. Science. 2009;324:1068–71. [PMC free article] [PubMed] f1000 Factor 10.0 Exceptional
Simon Gilroy 01 May 2009, Ramon Serrano 11 May 2009, Daniel Gallie 13 Aug 2009, Judy Callis 26 Aug 2009
15. Nishimura N, Sarkeshik A, Nito K, Park SY, Wang A, Carvalho PC, Lee S, Caddell DF, Cutler SR, Chory J, Yates JR, Schroeder JI. PYR/PYL/RCAR family members are major in-vivo ABI1 protein phosphatase 2C-interacting proteins in Arabidopsis. Plant J. 2010;61:290–9. [PMC free article] [PubMed] f1000 Factor 3.2 Recommended
Evaluated by Jörg Kudla 02 Dec 2009, Judy Callis 07 Jan 2010
16. Santiago J, Rodrigues A, Saez A, Rubio S, Antoni R, Dupeux F, Park SY, Márquez JA, Cutler SR, Rodriguez PL. Modulation of drought resistance by the abscisic acid receptor PYL5 through inhibition of clade A PP2Cs. Plant J. 2009;60:575–88. doi: 10.1111/j.1365-313X.2009.03981.x. [PubMed] [Cross Ref]
17. Ma Y, Szostkiewicz I, Korte A, Moes D, Yang Y, Christmann A, Grill E. Regulators of PP2C phosphatase activity function as abscisic acid sensors. Science. 2009;324:1064–8. [PubMed] f1000 Factor 8.2 Exceptional
Evaluated by Ramon Serrano 21 May 2009, Daniel Gallie 14 Aug 2009, Judy Callis 26 Aug 2009
18. Melcher K, Ng LM, Zhou XE, Soon FF, Xu Y, Suino-Powell KM, Park SY, Weiner JJ, Fujii H, Chinnusamy V, Kovach A, Li J, Wang Y, Li J, Peterson FC, Jensen DR, Yong EL, Volkman BF, Cutler SR, Zhu JK, Xu HE. A gate-latch-lock mechanism for hormone signalling by abscisic acid receptors. Nature. 2009;462:602–8. doi: 10.1038/nature08613. [PMC free article] [PubMed] [Cross Ref] f1000 Factor 6.4 Must Read
Evaluated by Michael Blatt 11 Dec 2009, Judy Callis 07 Jan 2010
19. Miyazono K, Miyakawa T, Sawano Y, Kubota K, Kang HJ, Asano A, Miyauchi Y, Takahashi M, Zhi Y, Fujita Y, Yoshida T, Kodaira KS, Yamaguchi-Shinozaki K, Tanokura M. Structural basis of abscisic acid signalling. Nature. 2009;462:609–614. doi: 10.1038/nature08583. [PubMed] [Cross Ref]
20. Nishimura N, Hitomi K, Arvai AS, Rambo RP, Hitomi C, Cutler SR, Schroeder JI, Getzoff ED. Structural mechanism of abscisic acid binding and signaling by dimeric PYR1. Science. 2009;326:1373–9. doi: 10.1126/science.1181829. [PMC free article] [PubMed] [Cross Ref]
21. Santiago J, Dupeux F, Round A, Antoni R, Park SY, Jamin M, Cutler SR, Rodriguez PL, Márquez JA. The abscisic acid receptor PYR1 in complex with abscisic acid. Nature. 2009;462:665–8. doi: 10.1038/nature08591. [PubMed] [Cross Ref]
22. Yin P, Fan H, Hao Q, Yuan X, Wu D, Pang Y, Yan C, Li W, Wang J, Yan N. Structural insights into the mechanism of abscisic acid signaling by PYL proteins. Nat Struct Mol Biol. 2009;16:1230–6. doi: 10.1038/nsmb.1730. [PubMed] [Cross Ref]
23. Schaller GE, Bleecker AB. Ethylene-binding sites generated in yeast expressing the Arabidopsis ETR1 gene. Science. 1995;270:1809–11. doi: 10.1126/science.270.5243.1809. [PubMed] [Cross Ref]
24. Dharmasiri N, Dharmasiri S, Estelle M. The F-box protein TIR1 is an auxin receptor. Nature. 2005;435:441–5. doi: 10.1038/nature03543. [PubMed] [Cross Ref]
25. Kepinski S, Leyser O. The Arabidopsis F-box protein TIR1 is an auxin receptor. Nature. 2005;435:446–51. doi: 10.1038/nature03542. [PubMed] [Cross Ref] f1000 Factor 11.0 Exceptional
Evaluated by Patrick Masson 01 Jun 2005 Yunde Zhao 02 Jun 2005, Tai-ping Sun 07 Jun 2005, Philip Benfey 09 Jun 2005, Vivian Irish 10 Jun 2005, Wolf B Frommer 02 Aug 2005, Emmanuel Liscum 11 Jan 2006
26. Tan X, Calderon-Villalobos LI, Sharon M, Zheng C, Robinson CV, Estelle M, Zheng N. Mechanism of auxin perception by the TIR1 ubiquitin ligase. Nature. 2007;446:640–5. doi: 10.1038/nature05731. [PubMed] [Cross Ref] f1000 Factor 10.7 Exceptional
Evaluated by Emmanuel Liscum 16 Apr 2007, Christopher Schofield 16 Apr 2007, Anthony Means 17 Apr 2007, Christian Hardtke 18 Apr 2007, Tai-ping Sun 18 May 2007, Seth J Davis 31 Jul 2007
27. Murase K, Hirano Y, Sun TP, Hakoshima T. Gibberellin-induced DELLA recognition by the gibberellin receptor GID1. Nature. 2008;456:459–63. doi: 10.1038/nature07519. [PubMed] [Cross Ref] f1000 Factor 6.6 Must Read
Evaluated by Nathan Nelson 08 Dec 2008, Hao Wu 15 Dec 2008, Eric Lam 06 Jan 2009
28. Robert N, Merlot S, N'Guyen V, Boisson-Dernier A, Schroeder JI. A hypermorphic mutation in the protein phosphatase 2C HAB1 strongly affects ABA signaling in Arabidopsis. FEBS Lett. 2006;580:4691–6. doi: 10.1016/j.febslet.2006.07.047. [PubMed] [Cross Ref]
29. Vlad F, Rubio S, Rodrigues A, Sirichandra C, Belin C, Robert N, Leung J, Rodriguez PL, Laurière C, Merlot S. Protein phosphatases 2C regulate the activation of the Snf1-related kinase OST1 by abscisic acid in Arabidopsis. Plant Cell. 2009;21:3170–84. doi: 10.1105/tpc.109.069179. [PubMed] [Cross Ref]

Articles from F1000 Biology Reports are provided here courtesy of Faculty of 1000 Ltd