To Grow or Not to Grow: TOR and SnRK2 Coordinate Growth and Stress Response in Arabidopsis

For optimal growth, plants must tightly control the switch between stress responses and regrowth upon restoration of favorable conditions. In this issue of Molecular Cell, Wang et al., 2017Wang P. Zhao Y. Li Z. Hsu C.-C. Liu X. Fu L. Hou Y.-J. Du Y. Xie S. Zhang C. et al.Reciprocal regulation of the TOR kinase and ABA receptor balances plant growth and stress response.Mol. Cell. 2017; 69 (this issue): 100-112Abstract Full Text Full Text PDF PubMed Scopus (247) Google Scholar reveal that reciprocal regulation of growth-promoting TOR and stress-activated SnRK2 facilitates plant adaptation to environmental variations. For optimal growth, plants must tightly control the switch between stress responses and regrowth upon restoration of favorable conditions. In this issue of Molecular Cell, Wang et al., 2017Wang P. Zhao Y. Li Z. Hsu C.-C. Liu X. Fu L. Hou Y.-J. Du Y. Xie S. Zhang C. et al.Reciprocal regulation of the TOR kinase and ABA receptor balances plant growth and stress response.Mol. Cell. 2017; 69 (this issue): 100-112Abstract Full Text Full Text PDF PubMed Scopus (247) Google Scholar reveal that reciprocal regulation of growth-promoting TOR and stress-activated SnRK2 facilitates plant adaptation to environmental variations. The capacity to adapt to environmental variations is essential for sessile organisms such as plants. The phytohormone abscisic acid (ABA) is induced in response to adverse environmental conditions like drought or cold temperature, and it signals through the PYL family of receptors to inhibit growth and facilitate stress response (Cutler et al., 2010Cutler S.R. Rodriguez P.L. Finkelstein R.R. Abrams S.R. Abscisic acid: emergence of a core signaling network.Annu. Rev. Plant Biol. 2010; 61: 651-679Crossref PubMed Scopus (1964) Google Scholar). When nutrients are sufficient and environmental conditions are optimal, the target of rapamycin (TOR) promotes plant growth (Dobrenel et al., 2016Dobrenel T. Caldana C. Hanson J. Robaglia C. Vincentz M. Veit B. Meyer C. TOR signaling and nutrient sensing.Annu. Rev. Plant Biol. 2016; 67: 261-285Crossref PubMed Scopus (249) Google Scholar). Tight control of the switch between stress response and re-growth upon restoration of favorable conditions is critical for a plant's survival and optimal growth, and the molecular mechanisms that govern this process are of tremendous interest. In this issue of Molecular Cell, Wang et al., 2017Wang P. Zhao Y. Li Z. Hsu C.-C. Liu X. Fu L. Hou Y.-J. Du Y. Xie S. Zhang C. et al.Reciprocal regulation of the TOR kinase and ABA receptor balances plant growth and stress response.Mol. Cell. 2017; 69 (this issue): 100-112Abstract Full Text Full Text PDF PubMed Scopus (247) Google Scholar reveal one such elegant mechanism, connecting TOR-regulated growth and the ABA-dependent stress response. The authors show that reciprocal regulation between these two pathways is necessary for stress response as well as for recovery of growth when stress is eliminated. Some PYLs bind and inhibit PP2C phosphatases in the presence of ABA, which results in activation of the stress- and ABA-induced kinase SnRK2 and downstream stress signaling. However, other PYLs can inhibit PP2C in an ABA-independent manner; how these PYLs are kept inactive under conditions favoring growth is not clear. Using a quantitative phosphoproteomics approach to compare Arabidopsis seedlings treated with and without ABA, Wang et al. identify a serine residue (Ser114 in PYL4 and Ser119 in PYL1) that is located within the ABA-binding pocket of PYLs and is phosphorylated only in the absence of ABA. Phosphorylation of this serine occurs under normal growth conditions when ABA is absent and stress responses are suppressed. This residue is conserved in 121 PYLs from 12 different species of land plants, suggesting potential conservation of the phosphorylation. Wang et al. observe that substitution of a phosphomimetic at the site of this conserved PYL serine abolishes PP2C interaction with ABA-dependent PYLs as well as PP2C interaction with most ABA-independent PYLs. This suggests that in the absence of stress, both ABA-dependent and ABA-independent PYLs are kept inactive by phosphorylation of a conserved serine residue. The location of this phosphorylation site within the ABA-binding pocket of PYL presumably facilitates the switch between stress response and growth signaling, with accumulating ABA occluding the site in times of stress and phosphorylation preventing the binding of residual ABA during growth recovery. After testing numerous kinases as candidates, Wang et al. identify TOR complex 1 (TORC1) as the kinase for Ser119-PYL1. Compelling evidence from both in vitro kinase assays and in vivo experiments using RNAi and pharmacological inhibitors suggests that TORC1 is the unique kinase for the conserved serine in PYLs, phosphorylation of which suppresses ABA signaling. Indeed, inhibition of TORC1 partially activates ABA downstream signaling even in the absence of ABA. The authors further demonstrate that TOR phosphorylation of PYL is not only essential for suppressing stress signaling during normal growth, but is also necessary for the recovery of growth after stress is removed. TOR assembles two biochemically and functionally distinct protein complexes, TORC1 and TORC2, conserved from yeast to mammals (Wullschleger et al., 2006Wullschleger S. Loewith R. Hall M.N. TOR signaling in growth and metabolism.Cell. 2006; 124: 471-484Abstract Full Text Full Text PDF PubMed Scopus (4671) Google Scholar). There is no evidence for the existence of plant TORC2, but TORC1, containing Raptor and LST8 in addition to TOR, is conserved in plants (Dobrenel et al., 2016Dobrenel T. Caldana C. Hanson J. Robaglia C. Vincentz M. Veit B. Meyer C. TOR signaling and nutrient sensing.Annu. Rev. Plant Biol. 2016; 67: 261-285Crossref PubMed Scopus (249) Google Scholar). Two plant Raptor proteins play redundant roles in the function of TORC1. Furthermore, the best-studied substrate of mTORC1, S6 kinase 1 (S6K1), has two orthologs in plants, and antibodies specific for phospho-T389 in human can recognize phospho-T449/T455 in Arabidopsis S6K1/S6K2. Information on plant TORC1 substrates is otherwise scarce. Interestingly, the peptide sequence surrounding Ser119-PYL1 does not conform to motifs identified for mTOR substrates (Hsu et al., 2011Hsu P.P. Kang S.A. Rameseder J. Zhang Y. Ottina K.A. Lim D. Peterson T.R. Choi Y. Gray N.S. Yaffe M.B. et al.The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling.Science. 2011; 332: 1317-1322Crossref PubMed Scopus (812) Google Scholar). It will be interesting to see, once more TOR substrates are characterized in plants, whether this site represents an outlier or whether Arabidopsis TOR has a substrate recognition motif distinct from that of mammalian TOR. Not surprisingly, Wang et al. show PYL is rapidly dephosphorylated upon stress and ABA production, which is necessary for inhibition of plant growth. Furthermore, they show ABA suppresses TORC1 activity through phosphorylation of Raptor on Ser897 (Wang et al., 2017Wang P. Zhao Y. Li Z. Hsu C.-C. Liu X. Fu L. Hou Y.-J. Du Y. Xie S. Zhang C. et al.Reciprocal regulation of the TOR kinase and ABA receptor balances plant growth and stress response.Mol. Cell. 2017; 69 (this issue): 100-112Abstract Full Text Full Text PDF PubMed Scopus (247) Google Scholar). Phosphorylation of mammalian Raptor has been reported on several different sites by various kinases, with activating or inhibitory effects (Foster and Fingar, 2010Foster K.G. Fingar D.C. Mammalian target of rapamycin (mTOR): conducting the cellular signaling symphony.J. Biol. Chem. 2010; 285: 14071-14077Crossref PubMed Scopus (431) Google Scholar). The outcome of Ser897 phosphorylation of plant TOR appears unique, as it inhibits TORC1 activity by disrupting the complex formation, a mechanism not reported for the mammalian complex. The stress- and ABA-induced kinase SnRK2 is demonstrated to be responsible for Ser897-Raptor phosphorylation. Hence, nature seems to have devised a simple and intellectually satisfying mechanism to govern the switch between growth and stress response via reciprocal regulation between the TOR pathway and the SnRK2 pathway (Figure 1). Crosstalk between growth-promoting TOR signaling and stress-response pathways in plants is conceptually intuitive and had indeed been postulated previously (Dobrenel et al., 2016Dobrenel T. Caldana C. Hanson J. Robaglia C. Vincentz M. Veit B. Meyer C. TOR signaling and nutrient sensing.Annu. Rev. Plant Biol. 2016; 67: 261-285Crossref PubMed Scopus (249) Google Scholar). SnRK1, a subfamily of kinases related to the SnRK2 subfamily, is a plant homolog of the mammalian AMP-activated protein kinase (AMPK) (Halford and Hey, 2009Halford N.G. Hey S.J. Snf1-related protein kinases (SnRKs) act within an intricate network that links metabolic and stress signalling in plants.Biochem. J. 2009; 419: 247-259Crossref PubMed Scopus (263) Google Scholar). In mammals, AMPK senses energy deprivation and inhibits mTORC1, and one of the mechanisms of this inhibition is through AMPK phosphorylation of Raptor on Ser722/Ser792, which is then bound by the inhibitor 14-3-3 (Gwinn et al., 2008Gwinn D.M. Shackelford D.B. Egan D.F. Mihaylova M.M. Mery A. Vasquez D.S. Turk B.E. Shaw R.J. AMPK phosphorylation of raptor mediates a metabolic checkpoint.Mol. Cell. 2008; 30: 214-226Abstract Full Text Full Text PDF PubMed Scopus (2749) Google Scholar). In plants, SnRK1 is activated by nutrient starvation or metabolic stress, whereas TOR is most likely active under nutrient sufficiency conditions. It is tempting to speculate that there may be direct molecular connections between SnRK1 and TOR to coordinate their antagonistic roles on plant growth. Does SnRK1 phosphorylate Raptor and inhibit TORC1? If so, does the mechanism resemble phosphorylation by AMPK (phospho-Raptor recruiting an inhibitor) or by SnRK2 (disrupting the TORC1 complex)? Do other mediators of stress responses crosstalk with the TOR signaling pathway? Certainly, the findings of Wang et al., 2017Wang P. Zhao Y. Li Z. Hsu C.-C. Liu X. Fu L. Hou Y.-J. Du Y. Xie S. Zhang C. et al.Reciprocal regulation of the TOR kinase and ABA receptor balances plant growth and stress response.Mol. Cell. 2017; 69 (this issue): 100-112Abstract Full Text Full Text PDF PubMed Scopus (247) Google Scholar are just the tip of the iceberg. Future studies will undoubtedly continue to unveil the mechanisms of TOR as a master regulator. C.L.R. is an employee of Technical Resources International. Reciprocal Regulation of the TOR Kinase and ABA Receptor Balances Plant Growth and Stress ResponseWang et al.Molecular CellDecember 28, 2017In BriefWang et al. reveal that the TOR kinase phosphorylates ABA receptors to repress stress responses under unstressed conditions and to promote growth recovery once environmental stresses subside. Under stress conditions, SnRK2s phosphorylate Raptor, a regulatory component in the TOR complex, to prevent growth by inhibiting TOR activity. Full-Text PDF Open Archive