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Plant Science


Metabolic Regulation and Signalling

Principal Investigator: Dr Matthew J. Paul

Matthew Paul

Trehelose Pathway

Plants are the only organisms in which the pathways of both sucrose and trehalose synthesis are indispensable. Genes for the trehalose pathway are highly regulated to synthesise trehalose 6-P, trehalose in [µM] concentrations. Phenotypes of improved growth, resource use, stress tolerance can be produced when the trehalose pathway is modified. Until recently the mechanistic basis of these phenotypes was not known.

We have recently discovered that a major function of the trehalose pathway in plants is to regulate the use of sucrose in biosynthetic pathways associated with growth through trehalose 6-phosphate regulation of the feast/ famine central regulatory protein kinase, SnRK1 (AMPK, SNF1 group of protein kinases).
Zhang Y, Primavesi LF, Jhurreea D, Andralojc PJ, Mitchell RAC, Powers SJ, Schluepmann H, Delatte T, Wingler A, Paul MJ (2009) Inhibition of Snf1-related protein kinase (SnRK1) activity and regulation of metabolic pathways by trehalose 6-phosphate. Plant Physiology, 149, 1860-1871

Work on the trehalose pathway grew out of research on metabolic signalling. The rationale was to understand, modify and select for variation in central regulators of metabolism to improve processes important in crop yield such as photosynthesis, assimilate partitioning, biomass production and stress tolerance. Work has shown that it is possible to alter all of the above traits through modification of the trehalose pathway in plants. However, until recently the mechanistic basis for how the trehalose pathway could produce these effects was unclear.

This is important because understanding how plants regulate use of their carbon is key to understanding the regulation of growth and yield in different environments.

Current strategy and opportunities - understanding more of the biochemistry of interaction of T6P with SnRK1, including purification of protein component of SnRK1 complex with which T6P interacts - target T6P synthesis/ breakdown to improve crop performance (growth, yield, stress tolerance, biosynthetic pathways) of wheat and oilseed rape.

 

Inhibition of SnRK1 activity in vitro in extracts of seedlings of Arabidopsis thaliana (Zhang et al. 2009). 

SnRK1 is a member of a family of calcium-independent serine-threonine protein kinases which includes AMPK of mammals and SNF1 of yeast. They are conserved in eukaryotes and perform a fundamental role in transcriptional, metabolic and developmental regulation in response to energy limitation and starvation of carbon source. Recent work established that SnRK1 catalytic activity regulates a thousand or so target genes involved in the response of metabolism and growth to starvation (Baena-González et al. 2007). SnRK1 activates genes involved in degradation processes and photosynthesis and inhibits those involved in biosynthetic processes and, by so doing, regulates metabolism and growth in response to available carbon. Essentially, SnRK1 regulates feast/ famine responses in plants. By inhibiting SnRK1, T6P counters the starvation response and promotes the feast response i.e. growth and end-product synthesis through up regulation of genes involved in biosynthetic processes and growth important for crop productivity. Through defining a signalling route for T6P we have provided a mechanistic basis for the function and potency of T6P in plants (Zhang et al. 2009)

Inhibitionof SnRK1 activity by T6P in vivo

Inhibition of SnRK1 activity by T6P in vivo through analysis of SnRK1 marker gene expression in A. thaliana seedlings with genetically increased amounts of T6P (otsA, encoding an E. coli TPS) and genetically decreased amounts of T6P (otsB, encoding an E. coli TPP) (Zhang et al. 2009).

Model for the function of T6P in growing tissues

Trehalose pathway genes trehalose phosphate synthase (TPS) and trehalose phosphate phosphatase (TPP) are regulated highly cell specifically at the transcriptional level, responding to sugar supply and stress. Phosphorylation and interaction with 14-3-3 proteins has also been shown for TPS proteins.

In plants unlike other organisms, trehalose is not a major end-product (except in a few resurrection species). Hence, T6P is removed from major pathway flux and can fluctuate without compromising other functions unlike central intermediates (G6P, for example) which have a limited dynamic range. Sucrose has been shown to lead to a large (30-fold) and rapid (minutes to hours) increase in T6P levels (Lunn et al. 2006). Therefore, T6P could signal the availability of sucrose and thus inhibit SnRK1 activity and the starvation response that SnRK1 mediates to promote biosynthetic reactions. It is not known whether T6P responds to other sugars such as glucose and therefore whether T6P is a signal of general sugar status or specifically of sucrose status. Glucose mediates signalling through hexokinase-1, which regulates photosynthetic gene expression in particular. Interestingly, unlike T6P, which is synthesised from G6P and UDP-glucose, hexokinase-1 signalling occurs independently of hexose phosphates (Moore et al. 2003).

 

feast - high sucrose   Famine-low sucrose

Opportunities


   

We have shown that T6P promotes biosynthesis and growth. These are exactly the processes required for good crop yield. T6P can be seen as a regulator or switch that promotes anabolic processes. This could be used to improve the accumulation of end-products (starch, protein, lipid cell wall) in the harvested parts of crops. There is also a proven link between the trehalose pathway and stress tolerance, particularly drought. There is potential to utilise genetic variation in the trehalose pathway to modify T6P synthesis/ breakdown in specific cells and tissues to promote growth, end-product accumulation and stress tolerance.

Team members

Lucia Primavesi

Lucia Primavesi

Catia Nunes

Catia Nunes

Catia Nunes

Matthew Paul's Profile

Degrees in Agricultural Botany (BSc, Upper second, Bangor, University of Wales, 1984); Plant Biochemistry (PhD, University of Leicester, 1989)

Post-Doctoral Awards Royal Society European Post-Doctoral Fellowship, University of Bayreuth, Germany. Molecular physiology of plant carbohydrate metabolism

Expertise Carbohydrate metabolism and photosynthesis; plant growth and productivity; plant biochemistry/ physiology/ molecular physiology/ effect of environment; sugar signalling and trehalose pathway

Discoveries Mechanism of sugar signalling that relates sucrose supply to growth through trehalose 6-phosphate (T6P) regulation of the central feast/ famine stress regulator SnRK1 (SNF1-related protein kinase). T6P links plant sugar status to genes regulated by SnRK1 involved in plant growth and feast/ famine responses in growing tissues up regulating biosynthetic processes including end-product synthesis. This represents the basis for a mechanism where metabolism and carbon status are linked to growth and development. (Zhang Y, Primavesi LF, Jhurreea D, Andralojc PJ, Mitchell RAC, Powers SJ, Schluepmann H, Delatte T, Wingler A, Paul MJ 2009 Inhibition of Snf1-related protein kinase (SnRK1) activity and regulation of metabolic pathways by trehalose 6-phosphate. Plant Physiology, 149, 1860-1871).

Recent grants
2004-2007 Regulation of photosynthesis by phosphorus in Australia’s C3 and C4 tropical grasses. JP Conroy, S Von Caemmerer, MJ Paul. Australian Research Council. Co-PI
2005-2008 Integration of leaf metabolism by the trehalose pathway. BBSRC Responsive mode P&MS committee £211,394. Lead PI
006-2011 Trehalose signalling: understanding and exploiting an emerging small molecule carbohydrate paradigm. BBSRC SCIBS initiative £682,140. Lead PI
2008-2012 How does trehalose 6-phosphate signal plant vegetative growth and water deficit tolerance? Portuguese National Research Foundation. Co-PI
2010-2014 Promotion of yield and resource use efficiency of wheat through modification of the trehelose pathway. Lead PI

Active Collaborations

  • Dr Astrid Wingler (UCL)
  • Professor Ben Davis (Oxford University)
  • Professor Ten Feizi (Imperial College)
  • Dr Henriette Schluepmann (University of Utrecht)
  • Professor Pedro Fevereiro(University of Lisbon)
  • Professor Anabela Silva (University of Lisbon)

    Recent sabbatical visitors to Lab

  • Professor Eleazar Martinez, University of Mexico
  • Dr Astrid Wingler, University College London
  • Professor Jann Conroy, University of Western Sydney
  • Dr Oula Ghannoum, University of Western Sydney

    Selected key recent publications

    * Schluepmann H, Pellny T, van Dijken A, Smeekens S, Paul MJ (2003) Trehalose 6-phosphate is indispensable for carbohydrate utilisation and growth in Arabidopsis thaliana. Proceedings of National Academy of Sciences USA 100, 6849-6854

    - Pellny TK, Ghannoum O, Conroy JP, Schluepmann H, Smeekens S, Andralojc J, Krause K-P, Goddijn O, Paul MJ (2004) Genetic modification of photosynthesis with E.coli genes for trehalose synthesis. Plant Biotechnology Journal 2, 71-82

    * Schluepmann H, van Dijken A, Aghdasi M, Wobbes B, Paul M, Smeekens S (2004) Trehalose-mediated growth inhibition of Arabidopsis seedlings is due to trehalose-6-phosphate accumulation. Plant Physiology 135, 879-890

    * Kolbe A, Tiessen A, Schluepmann H, Paul MJ, Ulrich S, Geigenberger P (2005) Trehalose 6-phosphate regulates starch synthesis via post-translational activation of ADP-glucose pyrophosphorylase. Proceedings of the National Academy of Sciences USA 102, 11118-11123

    - Paul MJ (2007) Trehalose 6-phosphate. Current Opinion in Plant Biology 10, 303-309

    - Paul MJ, Primavesi L, Jhurreea D, Zhang Y (2008) Trehalose metabolism and signalling. Annual Review of Plant Biology 59, 417-441

    - Paul MJ (2008) Trehalose 6-phosphate - a signal of sucrose status. Biochemical Journal 412, e1-e2

    * Zhang Y, Primavesi LF, Jhurreea D, Andralojc PJ, Mitchell RAC, Powers SJ, Schluepmann H, Delatte T, Wingler A, Paul MJ (2009) Inhibition of Snf1-related protein kinase (SnRK1) activity and regulation of metabolic pathways by trehalose 6-phosphate. Plant Physiology 149, 1860-1871

    - Schluepmann H, Paul MJ (2009) Trehalose metabolites in Arabidopsis -elusive, active and central. The Arabidopsis Book doi: 10.1199/tab.0122: http://www.aspb.org/publications/arabidopsis.

    - Perez-Victoria I, Kemper S, Patel MK, Edwards J, Errey JC, Primavesi LF, Paul MJ, Claridge TDW, Davis BG (2009) Saturation transfer difference NMR reveals functionally essential kinetic differences for a sugar binding repressor protein. Chemical Communications 39, 5862-5864

    - Eleazar Martinez-Barajas, Thierry Delatte, Henriette Schluepmann, Gerhardus J. de Jong, Govert W. Somsen, Cátia Nunes, Lucia F. Primavesi, Patricia Coello, Rowan A.C. Mitchell, Matthew J. Paul (2011) Wheat grain development is characterised by remarkable trehalose 6-phosphate accumulation pre-grain filling: tissue distribution and relationship to SNF1-related protein kinase1 activity Plant Physiology, Published on March 14, 2011, as DOI:10.1104/pp.111.174524. http://www.plantphysiol.org/cgi/content/short/pp.111.174524?keytype=ref&ijkey=breGvhE8TKztYTI

    *Faculty of 1000 citations

    Other publications with over 100 citations

    - Pilon-Smits EAH, Ebskamp MJM, Paul MJ, Jeuken MJW, Weisbeek PJ, Smeekens SCM (1995) Functional significance of fructans in plants: improved performance of transgenic fructan-accumulating tobacco under drought stress. Plant Physiology 107, 125-130

    - Paul MJ, Driscoll SP (1997) Sugar repression of photosynthesis: the role of carbohydrates in signalling nitrogen deficiency through source:sink imbalance. Plant, Cell and Environment 20, 110-116

    - Paul MJ, Foyer CH (2001) Sink regulation of photosynthesis. Journal of Experimental Botany 52, 1383-1400

    Invited Recent Lectures

  • Trehalose 6-phosphate makes sugar sense. University of Sheffield 2008
  • Trehalose 6-phosphate makes sugar sense. University of York 2008
  • Inhibition of SNF1-related protein kinase1 activity and regulation of metabolic pathways by trehalose 6-phosphate. Protein Complexes in Signalling and Development meeting, University of Glasgow, 2009
  • Sugars and SnRK1 kinase and the versatility of sugar function in plants. Max Planck Institute of Molecular Plant Physiology, Golm, Germany, 2009
  • Sugars and SnRK1 protein kinase and the versatility of sugar function in plants. University of Utrecht, The Netherlands, 2010
  • How do sugars regulate plant growth?University of Oxford, 2010

    Local Honours

    Mayor’s Award for Citizenship (2007)

    Discoveries

    Trehalose 6-phosphate (T6P) is an inhibitor of central regulator SnRK1. T6P links plant sugar status to genes regulated by SnRK1 involved in plant growth and feast/ famine responses in growing tissues up regulating biosynthetic processes including end-product synthesis. This represents the basis for a mechanism where metabolism and carbon status are linked to growth and development.

    Scientific Publications

    • Eleazar Martinez-Barajas, Thierry Delatte, Henriette Schluepmann, Gerhardus J. de Jong, Govert W. Somsen, Cátia Nunes, Lucia F. Primavesi, Patricia Coello, Rowan A.C. Mitchell, Matthew J. Paul (2011) Wheat grain development is characterised by remarkable trehalose 6-phosphate accumulation pre-grain filling: tissue distribution and relationship to SNF1-related protein kinase1 activity Plant Physiology, Published on March 14, 2011, as DOI:10.1104/pp.111.174524. http://www.plantphysiol.org/cgi/content/short/pp.111.174524?keytype=ref&ijkey=breGvhE8TKztYTI
    • Paul MJ, Jhurreea D, Zhang Y, Primavesi L, Delatte T, Schluepmann H, Wingler A (2010) Up regulation of biosynthetic processes associated with growth by trehalose 6-phosphate. Plant Signaling and Behavior, in press
    • Paul MJ (2010) Photosynthetic carbon dioxide fixation. Encyclopedia of Biological Chemistry. Elsevier
    • Perez-Victoria I, Kemper S, Patel MK, Edwards J, Errey JC, Primavesi LF, Paul MJ, Claridge TDW, Davis BG (2009) Saturation transfer difference NMR reveals functionally essential kinetic differences for a sugar binding repressor protein. Chemical Communications, 39, 5862-5864.
    • Zhang Y, Primavesi LF, Jhurreea D, Andralojc PJ, Mitchell RAC, Powers SJ, Schluepmann H, Delatte T, Wingler A, Paul MJ (2009) Inhibition of Snf1-related protein kinase (SnRK1) activity and regulation of metabolic pathways by trehalose 6-phosphate. Plant Physiology, in press. http://www.plantphysiol.org/cgi/content/short/pp.108.133934?keytype=ref&ijkey=jzn9fUtMGycFLXb
    • Schluepmann H, Paul MJ (2009) Trehalose metabolites in Arabidopsis - elusive, active and central. The Arabidopsis Book, in press.
    • Paul MJ, Primavesi L, Jhurreea D, Zhang Y (2008) Trehalose metabolism and signalling. Annual Review of Plant Biology 59, 417-441. http://arjournals.annualreviews.org/eprint/mhkVABy78dXaZVcV5n2S/full/10.1146/annurev.arplant.59.032607.092945.
    • Ghannoum O, Paul M, Ward J, Beale M, Corol D-I, Conroy JP (2008) The sensitivity of photosynthesis to phosphorus deficiency differs between C3 and C4 tropical grasses. Functional Plant Biology 35, 213-221.
    • Paul MJ (2008) Trehalose 6-phosphate - a signal of sucrose status. Biochemical Journal 412, e1-e2.
    • Paul MJ, Primavesi L, Jhurreea D, Zhang Y (2008) Trehalose metabolism and signalling. Annual Review of Plant Biology 59, 417-441. http://arjournals.annualreviews.org/eprint/mhkVABy78dXaZVcV5n2S/full/10.1146/annurev.arplant.59.032607.092945.
    • Almeida AM, Silva AB, Araújo SS, Cardoso LA, Santos DM, Torné JM, Silva JM, Paul MJ, Fevereiro PS (2007) Responses to water withdrawal of tobacco plants genetically engineered with the AtTPS1 gene: a special reference to photosynthetic parameters. Euphytica 154, 113-126.
    • Paul MJ (2007) Trehalose 6-phosphate. Current Opinion in Plant Biology 10, 303-309.
    • Raines C, Paul MJ (2006) Products of leaf primary carbon metabolism modulate the developmental programme determining plant morphology. Journal of Experimental Botany 57, 1857-1862.
    • Kolbe A, Tiessen A, Schluepmann H, Paul M, Ulrich S, Geigenberger P (2005) Trehalose-6-phosphate regulates starch synthesis via post-translational redox-activation of ADP-glucose pyrophosphorylase. Proceedings of National Academy of Sciences 102, 11118-11123.
    • Pellny TK, Ghannoum O, Conroy JP, Schluepmann H, Smeekens S, Andralojc J, Krause K-P, Goddijn O, Paul MJ (2004) Genetic modification ofphotosynthesis with E.coligenes for trehalose synthesis. Plant Biotechnology Journal 2, 71-82.
    • Schluepmann H, van Dijken A, Aghdasi M, Wobbes B, Paul M, Smeekens S (2004) Trehalose-mediated growth inhibition of Arabidopsis seedlings is due to trehalose-6-phosphate accumulation. Plant Physiology 135, 879-890.
    • Paul MJ (2004) Photosynthetic carbon dioxide fixation. Encyclopedia of Biological Chemistry (WJ Lennarz, MD Lane, eds) Elsevier, Oxford, Vol 3, pp 336-341.
    • Schluepmann H, Pellny T, van Dijken A, Smeekens S, Paul MJ(2003) Trehalose 6-phosphate is indispensable for carbohydrate utilisation and growth in Arabidopsis thaliana. Proceedings of National Academy of Sciences 100, 6849-6854.
    • Paul MJ, Pellny TK (2003) Carbon metabolite feedback regulation of leaf photosynthesis and development. Journal of Experimental Botany 54, 539-547.
    • Halford NG, Paul MJ (2003) Carbon metabolite sensing and signalling. Plant Biotechnology Journal 1, 381-398.
    • Paul MJ, Lawlor DW (2003) Genetics of crop improvement: GM of primary metabolism- Photosynthesis. Encyclopedia of Applied Plant Sciences, 484-493.
    • Paul MJ, Pellny T, Goddijn O (2001) Enhancing photosynthesis with sugar signals. Trends in Plant Science 6, 197-200.
    • Paul MJ, Foyer CH (2001) Sink regulation of photosynthesis. Journal of Experimental Botany, 52 1383-1400.
    • Pieters A, Paul MJ,Lawlor DW (2001) Low sink demand limits photosynthesis under phosphate deficiency. Journal of Experimental Botany 52, 1083-1091.