Plant sugar sensing and signaling - a complex reality.

In plants, sugars function as a metabolic resource, but they are also important regulators of many processes associated with growth, maturation and senescence1xCarbohydrate-modulated gene expression in plants. Koch, K.E. Annu. Rev. Plant Physiol. Plant Mol. Biol. 1996; 47: 509–540CrossRef | PubMedSee all References, 2xSugar sensing in higher plants. Jang, J-C. and Sheen, J.S. Trends Plant Sci. 1997; 2: 208–214Abstract | Full Text PDFSee all References. Their regulatory activities include both the repression and activation of many genes, and it is probable that several distinct sensing and transduction mechanisms are involved2xSugar sensing in higher plants. Jang, J-C. and Sheen, J.S. Trends Plant Sci. 1997; 2: 208–214Abstract | Full Text PDFSee all References, 3xSugar sensing and sugar-mediated signal transduction in plants. Smeekens, S. and Rooks, F. Plant Physiol. 1997; 115: 7–13PubMedSee all References, 4xSucrose is a signal molecule in assimilate partitioning. Chiou, T-J. and Bush, D.R. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 4784–4788CrossRef | PubMed | Scopus (258)See all References. In response to a recent article by Nigel Halford and colleagues5xIs hexokinase really a sugar sensor in plants?. Halford, N.G., Purcell, P.C., and Hardie, D.G. Trends Plant Sci. 1999; 4: 117–120Abstract | Full Text | Full Text PDF | PubMed | Scopus (104)See all References5, which questioned whether hexokinase functions in sugar sensing and signaling, as well as in hexose metabolism, we consider evidence that substantiates this dual function. We also highlight some of the differences in sugar signaling between yeast and plants, which emphasize the unique ways in which plants have evolved to carry out their life cycle.Using both genetic and biochemical approaches, there is much available evidence that plant hexokinase-dependent glucose metabolism can be separated from hexokinase-dependent glucose signaling.Firstly, transformation of Arabidopsis for sense or antisense expression of AtHXK1 or AtHXK2 resulted in hyper- and hypo-sensitive plants, respectively, based on rbcs and cab gene expression and on seedling bioassays with exogenous sugars6xHexokinase as a sugar sensor in higher plants. Jang, J-C. et al. Plant Cell. 1997; 9: 5–19PubMedSee all References6. Importantly, this effect was not caused by altered HXK-dependent glucose metabolism, because Arabidopsis transformed with yeast HXK2 were actually less sensitive to glucose repression, in spite of a three- to fivefold increase in enzyme activity.Secondly, glucose analogs can arrest seed germination and/or seedling development by a mechanism that affects sugar signaling independently of hexose metabolism. For example, low levels of mannose can block germination of Arabidopsis without affecting seed levels of ATP or inorganic phosphate7xMannose inhibits Arabidopsis germination via a hexokinase-mediated step. Pego, J.V., Weisbeek, P.J., and Smeekens, S.C.M. Plant Physiol. 1999; 119: 1017–1023CrossRef | PubMedSee all References7, and mannose-dependent repression of germination can be overcome by mannoheptulose (a competitive inhibitor of hexokinase)7xMannose inhibits Arabidopsis germination via a hexokinase-mediated step. Pego, J.V., Weisbeek, P.J., and Smeekens, S.C.M. Plant Physiol. 1999; 119: 1017–1023CrossRef | PubMedSee all References7. Furthermore, germination in the presence of mannoheptulose indicates that hexose phosphorylation by hexokinase is not required for germination of Arabidopsis.Finally, glucose repression of gene expression has also been examined using freshly isolated mesophyll protoplasts. Co-transfection of hexokinase substrates, glucose analogs or intermediary metabolites with reporter genes, has demonstrated: gene specificity; a requirement for hexose phosphorylation; and the lack of inhibition by hexose-phosphates, other glycolytic intermediates, ATP or inorganic phosphate8xSugar sensing in higher plants. Jang, J.C. and Sheen, J.S. Plant Cell. 1994; 6: 1665–1679PubMedSee all References8.These and other available data (e.g. 3xSugar sensing and sugar-mediated signal transduction in plants. Smeekens, S. and Rooks, F. Plant Physiol. 1997; 115: 7–13PubMedSee all References, 9xCarbon catabolite repression regulates glyoxylate cycle gene expression in cucumber. Graham, I.A., Denby, K.J., and Leaver, C.J. Plant Cell. 1994; 6: 761–772PubMedSee all References) offer compelling and unequivocal evidence that plant hexokinase plays a major role in glucose-dependent modulation of gene expression and plant growth. The recent isolation of two AtHXK1 mutants has provided definitive evidence for such a role (L. Zhou et al., unpublished), but a complete understanding of this role awaits a detailed molecular determination of the encoded protein's putative signaling and metabolic functions. The isolation of suppressors in a plant hexokinase-null mutant, or the isolation of HXK mutants that can uncouple the two functions, will prove that the two roles are indeed separable.Recent research has indicated that sugar signaling in plants also occurs by a hexose-dependent but hexokinase-independent pathway10xGlucose and stress independently regulate source and sink metabolism and defense mechanisms via signal transduction pathways involving protein phosphorylation. Ehness, R. et al. Plant Cell. 1997; 9: 1825–1841PubMedSee all References10, as well as by a sucrose-dependent pathway4xSucrose is a signal molecule in assimilate partitioning. Chiou, T-J. and Bush, D.R. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 4784–4788CrossRef | PubMed | Scopus (258)See all References4. The existence of multiple pathways indicates that sugar-signal transduction processes are relatively complex in plants. It has recently been suggested that plant homologs of yeast SNF1 kinase mediate both hexose and sucrose signaling mechanisms, largely at the exclusion of any role for hexokinase5xIs hexokinase really a sugar sensor in plants?. Halford, N.G., Purcell, P.C., and Hardie, D.G. Trends Plant Sci. 1999; 4: 117–120Abstract | Full Text | Full Text PDF | PubMed | Scopus (104)See all References5. However, if these homologs are of central importance, then it remains to be explained why antisense expression of the gene in potato only appears to affect the expression of sucrose synthase5xIs hexokinase really a sugar sensor in plants?. Halford, N.G., Purcell, P.C., and Hardie, D.G. Trends Plant Sci. 1999; 4: 117–120Abstract | Full Text | Full Text PDF | PubMed | Scopus (104)See all References5.We believe that the unique properties of plant carbohydrate biochemistry, and its interface with multiple growth processes, will necessarily lead to different models for sugar signaling in plants compared with yeast. First, in yeast, glucose-dependent repression of gene expression involves prominent negative DNA regulatory elements that control the utilization of non-fermentable carbohydrates11xGlucose repression in fungi. Ronne, H. Trends Genet. 1995; 11: 12–17Abstract | Full Text PDF | PubMed | Scopus (321)See all References11. In contrast, plant sugar repression involves positive DNA regulatory elements, which in source tissues respond to inputs from carbohydrate biosynthesis (‘end-product inhibition’) and in sink tissues respond to carbohydrate utilization12xMetabolic repression of transcription in higher plants. Sheen, J.S. Plant Cell. 1990; 2: 1027–1038PubMedSee all References12. Second, the trafficking of sugars is very different in plant cells and yeast and, as such, the relationships between sugar signaling and sugar metabolism will also be different. Plant carbohydrate metabolism involves intracellular cycles, extensive compartmentation, and partitioning to, or from, organ-level transport processes13xSee all References13. All these processes are modulated by very sophisticated, diurnal regulatory programs. Finally, plant sugar signaling pathways can involve crosstalk with hormone signaling pathways that control growth and development and are unique to plants14xGlucose and ethylene signal transduction crosstalk revealed by an Arabidopsis glucose-insensitive mutant. Zhou, L. et al. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 10294–10299CrossRef | PubMed | Scopus (282)See all References14. This type of complex signaling network in a multicellular plant does not occur in the unicellular yeast. Thus, it might be inappropriate to largely restrict plant sugar signaling models to known paradigms for yeast sugar signaling5xIs hexokinase really a sugar sensor in plants?. Halford, N.G., Purcell, P.C., and Hardie, D.G. Trends Plant Sci. 1999; 4: 117–120Abstract | Full Text | Full Text PDF | PubMed | Scopus (104)See all References5. Rather, it might be better to recognize that evolutionary motifs often involve a ‘used once, borrowed twice’ scenario.