Brief description of research activities

Sugars are the primary products of plants and affect almost every aspect of plant development. The lab is studying how sugars affect plant development and physiology. We focus on the initial central sugar metabolism genes hexokinases (HXKs) and fructokinases (FRKs).

We isolated HXK and FRK genes and determined their biochemical characteristics and intracellular localization

The role of each of the HXK and FRK isozymes is explored by the use of sense and antisense transgenic plants.

In contrast to a 100 years old hypothesis that sugars open stomata, we discovered recently that sugars close stomata, and they do it via HXK. 

Based on this discovery we developed a method (registered as a patent) to create plants that save water.

Another major topic in the lab is the connection between sugar metabolism and vascular development. We found that specific FRKs play major roles in xylem and phloem development.

More recently, we discovered a new connection between sugar levels and plant water management.

 Publication list

Publications

1. Kassir Y., Granot D. and Simchen G. (1988).
IME1, a positive regulator gene of meiosis in Saccharomyces cerevisiae.
Cell 82: 853-862.
2. Granot D., Margolskee J. P. and Simchen G. (1989).
A long region upstream of the IME1 gene regulates meiosis in yeast.
Mol. Gen. Genet. 218: 308-314.
3. Granot D. and Snyder M. (1991).
Segregation of the nucleolus during mitosis in budding and fission yeast.
Cell Motility and Cytoskeleton 20: 47-54.
4. Granot D. and Snyder M. (1991).
Glucose induces cAMP-independent growth-related changes in stationary phase cells of Saccharomyces cerevisiae.
Proc. Natl. Acad. Sci. USA. 88: 5724-5728.
5. Granot D. and Snyder M. (1993).
Carbon source induces growth of stationary phase yeast cells, independent of carbon source metabolism.
Yeast 9: 465-479.
6. Nahon E., Atzmoni D., Zahavi A. and Granot D. (1995).
Mate selection in yeast: A reconsideration of the signals and the message encoded by them.
J. Theoretical Biology 172: 315-322.
7. Hadas R., Schaffer A., Miron D. Fogelman M. and Granot D. (1995).
PCR-generated molecular markers for the invertase gene and sucrose accumulation in tomato.
Theor. Appl. Genet. 9: 1142-1148. IF 3.29; Rank 23/190.
8. Dai N., Schaffer A., Petreikov M. and Granot D. (1995).
Cloning of Arabidopsis thaliana hexokinase cDNA by complementation of yeast cells.
Plant Physiology 108: 879-880.
9. Granot D. and Dai N. (1996).
The 5' untranslated region of Arabidopsis thaliana calmodulin cDNA is an independent cDNA containing an open reading frame.
Planta 198: 162-163.
10. Kanayama Y., Dai N., Granot D., Petreikov M., Schaffer A. and Bennett A. (1997).
Divergent fructokinase genes are differentially expressed in tomato.
Plant Physiology 113:1379-1384.
11. Granot D. and Dai N. (1997).
Sugar induced cell death in yeast is dependent on the rate of sugar phosphorylation as determined by Arabidopsis thaliana hexokinase.
Cell Death and Differentiation 4: 555-559.
12. Dai N., Schaffer A., Petreikov M. and Granot D. (1997).
Potato (Solanum tuberosum L.) fructokinase expressed in yeast exhibits inhibition by fructose of both in vitro enzyme activity and rate of cell proliferation.
Plant Science 128:191-197.
13. Kanayama Y., Granot D., Dai N., Petriekov M., Schaffer A., Powell A. and Bennett A.B. (1998).
Tomato fructokinases exhibit differential expression and substrate regulation.
Plant Physiology 117:85-90.
14. Aly R., Granot D., Mahler-Slasky Y., Halpern N., Dai. N. and Galun E. (1999).
Saccharomyces cerevisiae cells harboring the gene encoding sarcotoxin IA secrete a peptide that is toxic to plant pathogenic bacteria.
Protein Expr Purif 16:120-124.
15. Dai N., Schaffer A., Petreikov M., Shahak Y., Giller Y., Ratner K., Levine A. and Granot D. (1999).
Overexpression of Arabidopsis hexokinase in tomato plants inhibits growth, reduces photosynthesis and induces rapid senescence.
Plant Cell 11: 1253-1266.
16. Schaffer A., Petreikov M., Miron D., Fogelman M., Spiegelman M., Bnei-Moshe Z., Shen S., Granot D., Hadas R., Dai N., Levine I., Bar M., Friedman M., Pilowsky M. Gilboa N. and Chen L. (1999).
Modification of carbohydrate content in developing tomato fruit.
Hort Science 34: 1024-1027.
17. Menu T., Rothan C., Dai N., Petreikov M., Etienne C., Destrac- Irvine A., Schaffer A., Granot D. and Bérénice Ricard (2001).
Cloning and characterization of a cDNA encoding hexokinase from tomato.
Plant Science 160:209-218.
18. Petreikov M., Dai N., Granot D. and Schaffer A. (2001).
Characterization of native and yeast expressed tomato fructokinase enzymes.
Phytochemistry 58: 841-847.
19. Levine A., Belengh B., Damari-Weisler H. and Granot D. (2001).
Vesicle-associated membrane protein of Arabidopsis blocks Bax-induced apoptosis in yeast downstream of oxidative burst.
J Biol Chem 276: 46284-46289.
20. Yaniv Z., Granot D., Lev E. and Schafferman D. (2002).
Biodiversity and uses of white mustard (Sinapis alba L.) native to Israel, as a plant with economic potential.
Journal of Herbs, Spices & Medicinal Plants 9:319-327.
21. Miron D., Petriekov M., Carmi N., Shen S., Levin I., Granot D., Zamski E. and Schaffer A. (2002).
Sucrose uptake, invertase localization and gene expression in developing fruit of L. esculentum and the sucrose- accumulating L. hirsutum.
Physiologia Plantarum 115:35-47.
22. Dai N., German M., Matsevitz T., Hanael R., Swartzberg D., Yeselson Y., Petreikov M., Schaffer A. A. and Granot D. (2002).
LeFRK2, the gene encoding the major fructokinase in tomato fruits, is not required for starch accumulation in developing fruits.
Plant Science 162:423-430.
23. Silber A., Ben-Jaacov J. , Ackerman A., Bar-Tal A., Levkovitch I., Matsevitz-Yosef T., Swartzberg D., Riov J. and Granot D. (2002).
Interrelationship between phosphorus toxicity and sugar metabolism in Verticordia plumosa L.
Plant and Soil 245: 249-260.
24. Dai N., Kandel M., Petreikov M., Hanael R., Levin I., Ricard B., Rothan C., Schaffer A.A. and Granot D. (2002).
The tomato hexokinase LeHXK1: cloning, mapping, expression pattern and phylogenetic relationships.
Plant Science 163: 581-590.
25. German M.A., Dai N., Chmelnitsky I., Sobolev I., Salts Y., Barg R., Schaffer A.A. and Granot D. (2002).
LeFRK4, a novel tomato (Lycopersicon esculentum L.) fructokinase specifically expressed in stamens.
Plant Science 163:607-613.
26. Carmi N., Zhang G., Petreikov M., Gao.Z., Eyal Y., Granot D. Schaffer A. A. (2003).
Cloning and functional expression of alkaline a- galactosidase from melon fruit: similarity to plant SIP proteins uncovers a novel family of plant glycosyl hydrolases.
Plant Journal 33:97-106.
27. German M.A., Kandel-Kfir M, Swartzberg D., Matsevitz T. and Granot D. (2003)
A rapid method for the analysis of zygosity in transgenic plants.
Plant Science 164:183-187.
28. German M., Dai N., Matsevitz T., Hanael R., Petreikov M., Bernstein N., Ioffe M., Shahak Y., Schaffer A.A. and Granot D. (2003).
Suppression of fructokinase encoded by LeFRK2 in tomato stem inhibits growth and causes wilting of young leaves.
Plant Journal 34:837-846.
29. Granot D., Levine A. and Dor-Hefetz E. (2003).
Sugar-induced apoptosis in yeast cells.
FEMS Yeast Research 4:7-13.
Faculty of 1000 Biology: evaluations for Granot D. et al., FEMS Yeast Res 2003 Oct 4 (1) :7-13 http://www.f1000biology.com/article/id/1016810/evaluation
30. Roessner-Tunali U., Hegemann B., Carrari F., Lytovchenko A., Bruediga M. C., Granot D. and Fernie A. R. (2003).
Metabolic profiling of transgenic tomato plants overexpressing hexokinase reveals that the influence of hexose phosphorylation diminishes during fruit development.
Plant Physiology 133:84-99.
31. Butowt R., Granot D. and Rodríguez-García M. I. (2003).
A putative plastidic glucose translocator is expressed in heterotrophic tissues that do not contain starch, during olive (Olea europea L.) fruit ripening.
Plant Cell Physiology 44:1152-1161.
32. Menu T, Saglio P, Granot D, Dai N., Raymond P. and Ricard B (2003).
High hexokinase activity in tomato fruit perturbs carbon and energy metabolism and reduces fruit and seed size
Plant Cell and Environment 27:89-98.
33. German M.A., Asher I., Petreikov M., Dai N., Schaffer A. A. and Granot D. (2004).
Cloning, expression and characterization of LeFRK3, the fourth tomato (Lycopersicon esculentum Mill.) gene encoding fructokinase.
Plant Science 166:285-291.
34. Moing A., Maucourt M., Renaud C., Gaudillère M., Brouquisse R., Lebouteiller B., Gousset-Dupont A., Vidal J., Granot D., Denoyes-Rothan B., Lerceteau-Köhler E. and Rolin D. (2004).
Quantitative metabolic profiling through one-dimensional 1H NMR analyses: application to plant genetics and functional genomics
Functional Plant Biology 31: 889-902.
35. Swartzberg D., Dai N., Gan S., Amasino R. and Granot D. (2006).
Effects of cytokinin production under two SAG promoters on senescence and development of tomato plants.
Plant Biology 8:579-586.
36. Kandel-Kfir M.‚ Damari- Weissler H., German M. A., Gidoni D., Mett A., Belausov E., Petreikov M.‚ Adir N. and D. Granot (2006).
Two newly identified membrane- associated and plastidic tomato HXKs: characteristics, predicted structure and intracellular localization.
Planta 224: 1341-52.
37. Damari-Weissler H., Kandel- Kfir M., Gidoni D., Mett A., Belausov E., Granot D. (2006).
Evidence for intracellular spatial separation of hexokinases and fructokinases in tomato plants.
Planta 224:1495-1502.
38. Wigoda N., Ben-Nissan G., Granot D., Schwartz A. and Weiss D. (2006).
The gibberellin-induced, cysteine-rich protein GIP2 from Petunia hybrida exhibits in-planta antioxidant activity.
Plant Journal 48: 796-805.
39. Damari-Weissler H., Kandel- Kfir M., Gidoni D., Mett A., Krassovskaya I., Weber A. P.M., Belausov E., Granot D. (2007).
Spinach SoHXK1 is a mitochondria-associated hexokinase.
Planta 226:1053-1058.
40. Swartzberg D., Kirshner B., Rav-David D., Elad Y. and Granot D. (2008).
Botrytis cinerea induces senescence and is inhibited by autoregulated expression of the IPT gene.
European Journal of Plant Pathology 120: 289-297.
41. Granot D. (2008).
Putting plant hexokinases in their proper place.
Phytochemistry 69: 2649-54.
42. Damari-Weissler H., Rachamilevitch S., Aloni R., German M.A., Cohen S., Zwieniecki M.A., Holbrook N.M. and Granot D. (2009). LeFRK2 is required for phloem and xylem differentiation and the transport of both sugar and water.
Planta 230: 795-805.
43. Kroupitski Y., Golberg D., Belausov E., Pinto R., Swartzberg D., Granot D., and Sela S. (2009).
Internalization of Salmonella in leaves is induced by light and involves chemotaxis and penetration through open stomata.
Applied and Environmental Microbiology 75:6076-6086.
44. Swartzberg D., Hanael R. and Granot D. (2010).
Relationship between hexokinase and cytokinin in the regulation of leaf senescence and seed germination.
Plant Biology 13:439-44.
45. Granot-Hershkovitz E., Raas-Rothschild A., Frumkin A., Granot D., Silverstein S., Abeliovich D. (2011).
Complex Chromosomal Rearrangement in a Psychomotor-Retarded Girl and a de novo Inversion: inv(2)( q15;p24.2).
Am J Med Genet 155A:1825-1832.
46. Goren S., Huber S.C. and Granot D. (2011).
Evidence of developmental coordination of sucrose synthase isozymes in tomato plants.
Planta 233:1011-1023.
47. Dai N., CohenS. , Portnoy V., Tzuri G., Baja R., Pompan-Lotan M., Carmi N., Zhang G., Diber A., Pollock S., Karchi H., Yeselson L., Petreikov M., Shen S., Sahar U., Hovav R., Lewinsohn E., Tadmor Y., Granot D., Ophir R., Sherman A., Fei Z., Giovannoni J., Burger Y., Katzir N., Schaffer A.A. (2011).
Metabolism of soluble sugars in developing melon fruit: A global transcriptional view of the metabolic transition to sucrose accumulation.
Plant Mol Biol 76:1-18.
48. Castello, M.J., Carrasco, J.L., Navarrete-Gomez, M., Daniel, J., Granot, D., and Vera, P. (2011).
A plant small polypeptide is a novel component of DNA-binding protein phosphatase 1-mediated resistance to plum pox virus in Arabidopsis.
Plant Physiol. 157: 2206-2215.
49. Kelly, G., David-Schwartz, R., Sade, N., Moshelion, M., Levi, A., Alchanatis, V., and Granot, D. (2012).
The pitfalls of transgenic selection and new roles of AtHXK1: high level of AtHXK1 expression uncouples hexokinase1-dependent sugar signaling from exogenous sugar.
Plant Physiology 159: 47-51.
50. David-Schwartz R., Weintraub L., Vidavski R., Zemach H., Murakhovsky L., Swartzberg D. and Granot D. (2013).
The LeFRK4 promoter is active only during late stages of pollen and anther development
Plant Science 199-200: 61-70.
51. Kelly G., Moshelion M., David-Schwartz R., Halperin O., Wallach R., Attia Z., Belausov E., Granot D. (2013).
Hexokinase mediates stomatal closure.
Plant J 75: 977-988
F1000Prime Recommended this article as being of special significance in its field; http://f1000.com/prime/718017597?bd=1&ui=113252
DOI: 10.3410/f.718017597.793484554. F1000Prime.com/718017597#eval793484554
52. Kelly, G., Sade, N., Attia, Z., Secchi, F., Zwieniecki, M., Holbrook, N.M., Levi, A., Alchanatis, V., Moshelion, M., and Granot, D. (2014). Relationship between hexokinase and the aquaporin PIP1 in the regulation of photosynthesis and plant growth.
PloS One 9, e87888.
53. Sade N, Shatil-Cohen A, Attia Z, Maurel C, Boursiac Y, Kelly G, Granot D, Yaaran A, Lerner S, Moshelion M. (2014).
The role of plasma membrane aquaporins in regulating the bundle sheath-mesophyll continuum and leaf hydraulics.
Plant Physiol 166: 1609-20
54. Lawson T, Simkin AJ, Kelly G, Granot D. (2014).
Mesophyll photosynthesis and guard cell metabolism impacts on stomatal behaviour.
New Phytol 203: 1064-1081
55. Mukherjee T., Ivanova M., Dagda M., Kanayama Y., Granot D. and Holaday S.A. (2015).
Constitutively over-expressing a tomato fructokinase gene (LeFRK1) in cotton, Gossypium hirsutum L., (c.v. Coker 312) positively affects plant vegetative growth, boll number, and seed cotton yield.
Functional Plant Biology 42: 899-908.
56. Misra, B.B., Acharya, B.R., Granot, D., Assmann, S.M., and Chen, S. (2015).
The guard cell metabolome: functions in stomatal movement and global food security.
Front Plant Sci 6: 334.
57. Lugassi, N., Kelly, G., Fidel, L., Yaniv, Y., Attia, Z., Levi, A., Alchanatis, V., Moshelion, M., Raveh, E., Carmi, N., and Granot, D. (2015).
Expression of Arabidopsis hexokinase in citrus guard cells controls stomatal aperture and reduces transpiration.
Frontiers in Plant Science 6. DOI: 10.3389/fpls.2015.01114
58. Stein, O., Damari-Weissler, H., Secchi, F., Rachamilevitch, S., German, M.A., Yeselson, Y., Amir, R., Schaffer, A., Holbrook, N.M., Aloni, R., Zwieniecki, M.A., and Granot, D. (2016).
The tomato plastidic fructokinase SlFRK3 plays a role in xylem development.
New Phytol. 209: 1484-1495.
59. Stein, O., Avin-Wittenberg T., Krahnert I., Zemach H., Bogol V., Daron O., Aloni R., Fernie A. R. and Granot D. (2017).
Arabidopsis fructokinases are important for seed oil accumulation and vascular development.
Front Plant Sci 7: 2047
60. Kelly G., Sade N., Doron-Faigenboim A., Lerner S., Shatil-Cohen A., Yeselson Y., Egbaria A., Kottapalli J., Schaffer A.A., Moshelion M. and Granot D. (2017).
Sugar and hexokinase suppress expression of PIP aquaporins and reduce leaf hydraulics that preserves leaf water potential.
The Plant Journal 91, 325-339.
61. Kelly G., Lugassi N., Belausov E., Wolf D., Khamaisi B., Brandsma D., Kottapalli J., Fidel L., Ben-Zvi B., Egbaria A., Acheampong A.K., Zheng C., Or E., Distelfeld A., David-Schwartz R., Carmi C. and Granot D. (2017).
The Solanum tuberosum KST1 partial promoter as a tool for guard-cell expression in multiple plant species
J. Exp. Biol. DOI: https://doi.org/10.1093/jxb/erx159
62. Stein O., Secchi F., German, M.A., Damari-Weissler H., Aloni R., Holbrook N.M., Zwieniecky M.A. and Granot D. (2017).
The tomato cytosolic fructokinase FRK1 is important for phloem fiber development.
Biologia Plantarum DOI: 10.1007/s10535-017-0762-3
63. Goren, S., Lugassi, N., Stein, O., Yeselson, Y., Schaffer, A. A., David-Schwartz, R. and Granot, D. (2017).
Suppression of sucrose synthase affects auxin signaling and leaf morphology in tomato.
PLOS ONE 12, e0182334
64. Stein, O. and Granot, D. (2018).
Plant Fructokinases: Evolutionary, Developmental, and Metabolic Aspects in Sink Tissues.
Frontiers in Plant Science 9: 339 DOI: 10.3389/fpls.2018.00339
65. Halpern M., Bar-Tal A., Lugassi N., Egbaria A., Granot D. and Yermiyahu U. (2018).
The role of nitrogen in photosynthetic acclimation to elevated [CO2] in tomatoes.
Plant and Soil 434: 397-411
66. Kottapalli K., David-Schwartz R., Khamaisi B., Brandsma D., Lugassi N., Egbaria A., Kelly G. and Granot D. (2018).
Sucrose-induced stomatal closure is conserved across evolution.
PlosOne 13(10): e0205359
67. Mukherjee T., Gitz III D. C., Payton P., Kanayama Y., Granot D., and Holaday S. A. (2018).
Does overexpression of tomato fructokinase (LeFRK1) in cotton enhance yield?
The Journal of Cotton Science 22: 183-190
68. Stein O. and Granot D. (2019).
An overview of sucrose synthases in plants.
Frontiers in Plant Science 10: 95
69. Granot, D. and Kelly, G. (2019)
Evolution of Guard-Cell Theories: The Story of Sugars.
Trends Plant Science. DOI: 10.1016/j.tplants.2019.02.009

Invited Reviews
1. Granot D. (2007).
Role of tomato hexose kinases.
Functional Plant Biology 34:564-570 (including the volume cover page picture)
(Jennifer Henry, Editor, FPB and Alison Smith, Guest Editor).
2. Granot D., David-Schwartz R. and Kelly G. (2013).
Hexose kinases and their role in sugar-sensing and plant development.
Front Plant Sci 4: 44
3. Granot, D., Kelly, G., Stein, O., and David-Schwartz, R. (2014). Substantial roles of hexokinase and fructokinase in the effects of sugars on plant physiology and development. J Exp Bot 65: 809-819.
4. David-Schwartz R. Stein H., Raveh E., Granot D., Carmi N., and Klein T. (2019).
How woody plants respond to drought stress?
In: Stress Physiology of Woody Plants (in press)

Book Chapter
Granot D. (2008).
Sugar metabolism and signaling in plants. In " A Transgenic Approach to Plant Biochemistry and Physiology" Editors: Marisela Rivera-Domínguez, Rosalba-Troncoso Rojas and Martín Ernesto Tiznado-Hernández pp 51-72 Kerala, India

Patent applications
1. Carmi N., Petreikov M., Granot D., Eyal Y., Schaffer A.A.
Nucleotide sequences encoding for novel plant alkaline alpha-galactosidases
U.S.A. patent 2005/0208520 A1
2. Granot D., Swartzberg D. and German M.A.
Plant gene promoter and its use.
United States Patent and Trade Mark Office. Application no. PCT/IL2007/0004 000407
3. Granot D., German M.A., David-Schwartz R., Dai N., Schaffer A. and Petreikov M.
Use of fructokinases for increasing cell wall content.
United States Patent and Trade Mark Office. Application no. 61/560,303
4. Granot D. Gilor K. and Moshelion M.
Method for controling plant stomata aperture.
United States Patent and Trade Mark Office. Application no. 61/569,259
Granot D. Gilor K. and Moshelion M.
Methods of modulating stomata conductance and plant expression constructs for executing same.
Publication number: WO2013/088438; Application number: PCT/IL2012/050519
5. Granot D. and Stein O.
Methods for modifying oil content in plants and plants produced thereby.
US Provisional Patent Application No. 62/427,301 Filed on 29 November 2016.