Adolfo Saiardi Research Group

1989 Bsc University of Calabria, Cosenza Italy
1994 PhD Universita' La Sapienza Rome Italy
Adolfo Saiardi
Tel: 020 7679 7254
Fax: 020 7679 7805
Previous Posts: 
1995-1998 Postdoctoral Fellow IGBMC Strasbourg, France
1999-2002 Postdoctoral Fellow Johns Hopkins University Baltimore USA
2002-2004 Research Associate Johns Hopkins University Baltimore USA

The hexagonal inositol molecule serves as a module for the generation of a high level molecular diversity through the combinatorial attachment and removal of phosphate groups. Although, likely many of the observed inositol polyphosphates species merely represent metabolic intermediates, undoubtedly evolution has exploited this great diversity of structures by generating many important signalling molecules. Several phosphorylated derivatives of inositol are present in eukaryotic cells.

Adolfow1_0.jpg

The best characterized of them is the calcium releasing factor I(1,4,5)P3 (IP3), which represents a classical example of signal transduction mechanism; for IP3:

 

  • we know the stimuli that dynamically modulate its intracellular concentration;
  • we know the molecular mechanism of action;
  • we know the physiological consequence.

For none of the other inositol polyphosphates a specific function can be definitively and undoubtedly attributed, as none of them satisfies all the three criteria. Our objective is to characterize the physiological role of inositol polyphosphates that are still "orphan" of some (of all) of the three criteria described above. We are particularly interested to study the function of inositols containing high-energy pyrophosphate bonds. In fact, inositol ring is altered in a vast combinatorial array of possibilities, not only by adding phosphates, but also by the presence of two (pyro) or even three phosphate groups attached to different positions of ring. The best characterized inositol pyrophosphates are the diphosphoinositol pentakisphosphate (IP7 or PP-IP5) and the bis-diphosphoinositol tetrakisphosphate (IP8 or [PP]2-IP4). IP7 and IP8 are present in all eukaryotic cells analyzed thus far, from amoeba to mammalian neurons, and the enzymes responsible for their synthesis are highly conserved throughout evolution. Adolfow2_0.jpgThe high-energy bonds present in IP7 and IP8 have the potential for unprecedented molecular actions and their unique structure suggests that inositol pyrophosphates may represent a new class of second messengers with basic and not yet fully characterized functions. Our recent discovery that the high-energy phosphate of the pyrophosphate moiety can be directly donated to pre-phosphorylated proteins, providing a novel kind of protein post-transductional modification (protein pyrophosphorylation), may potentially open an entirely new and unexplored field in signal transduction.

Undoubtedly, evolution used the inositol module to create different signaling entities metabolically interconnected. The aim of my laboratory is to understand how an ancient inositol polyphosphates module with limited functions has evolved to become the sophisticated system of signaling molecules present in our cells.

Lab Members: 
Cristina Azevedo
Bernadett Kolozsvari
Publications
Jump to: 2014 | 2013 | 2012 | 2011 | 2010 | 2009 | 2008 | 2007 | 2006 | 2005 | 2004 | 2003 | 2002 | 2001 | 2000 | 1999 | 1998 | 1997 | 1995 | 1994 | 1993 | 1992 | 1990
Number of items: 73.

2014

Azevedo, C; Saiardi, A; (2014) Functions of inorganic polyphosphates in eukaryotic cells: a coat of many colours. Biochem Soc Trans , 42 (1) 98 - 102. 10.1042/BST20130111.

Djordjevic, JT; Lev, S; Li, C; Saiardi, A; Desmarini, D; Chayakulkeeree, M; ... Sorrell, T; + view all (2014) A novel branch of phospholipase C1-mediated signalling via inositol polyphosphate kinases, is essential for fungal virulence. MYCOSES , 57 13 - 13.

Kolozsvari, B; Parisi, F; Saiardi, A; (2014) Inositol phosphates induce DAPI fluorescence shift. Biochem J 10.1042/BJ20140237.

Li, CZJ; Lev, S; Saiardi, A; Desmarini, D; Sorrell, T; Djordjevic, JT; (2014) Role of the inositol polyphosphate kinases, Ipk1 and Asp1, in the pathogenesis of Cryptococcus neoformans. MYCOSES , 57 73 - 73.

Yu, J; Saiardi, A; Greenwood, JS; Bewley, JD; (2014) Molecular and biochemical identification of inositol 1,3,4,5,6-pentakisphosphate 2-kinase encoding mRNA variants in castor bean (Ricinus communis L.) seeds. Planta 10.1007/s00425-014-2028-z.

2013

Burton, A; Azevedo, C; Andreassi, C; Riccio, A; Saiardi, A; (2013) Inositol pyrophosphates regulate JMJD2C-dependent histone demethylation. PNAS , 110 (47) 18970 - 18975. 10.1073/pnas.1309699110.

Loss, O; Wu, CT; Riccio, A; Saiardi, A; (2013) Modulation of inositol polyphosphates levels regulates neuronal differentiation. Mol Biol Cell 10.1091/mbc.E13-04-0198.

Wilson, MS; Livermore, TM; Saiardi, A; (2013) Inositol pyrophosphates: between signalling and metabolism. Biochem J , 452 (3) 369 - 379. 10.1042/BJ20130118.

2012

Bosch, D; Saiardi, A; (2012) Arginine transcriptional response does not require inositol phosphate synthesis. J Biol Chem , 287 (45) 38347 - 38355. 10.1074/jbc.M112.384255.

Saiardi, A; (2012) How inositol pyrophosphates control cellular phosphate homeostasis? Advances in Biological Regulation , 52 (2) 351 - 359. 10.1016/j.jbior.2012.03.002. Green and gold open access
file

Saiardi, A; (2012) Cell signalling by inositol pyrophosphates. Subcell Biochem , 59 413 - 443. 10.1007/978-94-007-3015-1_14.

2011

Azevedo, C; Szijgyarto, Z; Saiardi, A; (2011) The signaling role of inositol hexakisphosphate kinases (IP6Ks). Adv Enzyme Regul , 51 (1) 74 - 82. 10.1016/j.advenzreg.2010.08.003.

Fassetti, F; Leone, O; Palopoli, L; Rombo, SE; Saiardi, A; (2011) IP6K gene identification in plant genomes by tag searching. BMC Proc , 5 Suppl 2 S1 - ?. 10.1186/1753-6561-5-S2-S1.

Lonetti, A; Szijgyarto, Z; Bosch, D; Loss, O; Azevedo, C; Saiardi, A; (2011) Identification of an evolutionarily conserved family of inorganic polyphosphate endopolyphosphatases. J Biol Chem , 286 (37) 31966 - 31974. 10.1074/jbc.M111.266320.

Loss, O; Azevedo, C; Szijgyarto, Z; Bosch, D; Saiardi, A; (2011) Preparation of quality inositol pyrophosphates. J Vis Exp (55) e3027 - ?. 10.3791/3027.

Maag, D; Maxwell, MJ; Hardesty, DA; Boucher, KL; Choudhari, N; Hanno, AG; ... Resnick, AC; + view all (2011) Inositol polyphosphate multikinase is a physiologic PI3-kinase that activates Akt/PKB. Proc Natl Acad Sci U S A , 108 (4) 1391 - 1396. 10.1073/pnas.1017831108.

Nagata, E; Saiardi, A; Tsukamoto, H; Okada, Y; Itoh, Y; Satoh, T; ... Takagi, S; + view all (2011) Inositol hexakisphosphate kinases induce cell death in Huntington disease. J Biol Chem , 286 (30) 26680 - 26686. 10.1074/jbc.M111.220749.

Szijgyarto, Z; Garedew, A; Azevedo, C; Saiardi, A; (2011) Influence of inositol pyrophosphates on cellular energy dynamics. Science , 334 (6057) 802 - 805. 10.1126/science.1211908.

2010

Andreassi, C; Zimmermann, C; Mitter, R; Fusco, S; Devita, S; Saiardi, A; Riccio, A; (2010) An NGF-responsive element targets myo-inositol monophosphatase-1 mRNA to sympathetic neuron axons. NAT NEUROSCI , 13 (3) 291 - U6. 10.1038/nn.2486.

Azevedo, C; Burton, A; Bennett, M; Onnebo, SM; Saiardi, A; (2010) Synthesis of InsP7 by the Inositol Hexakisphosphate Kinase 1 (IP6K1). Methods Mol Biol , 645 73 - 85. 10.1007/978-1-60327-175-2_5.

Azevedo, C; Saiardi, A; (2010) Reply to Shears: As knowledge of inositol pyrophosphates advances, wonder recedes. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA , 107 (5) E18 - E18. 10.1073/pnas.0914711107.

Nagata, E; Saiardi, A; Tsukamoto, H; Satoh, T; Itoh, Y; Itoh, J; ... Takagi, S; + view all (2010) Inositol hexakisphosphate kinases promote autophagy. Int J Biochem Cell Biol , 42 (12) 2065 - 2071. 10.1016/j.biocel.2010.09.013.

2009

Azevedo, C; Burton, A; Ruiz-Mateos, E; Marsh, M; Saiardi, A; (2009) Inositol pyrophosphate mediated pyrophosphorylation of AP3B1 regulates HIV-1 Gag release. P NATL ACAD SCI USA , 106 (50) 21161 - 21166. 10.1073/pnas.0909176106.

Burton, A; Hu, XW; Saiardi, A; (2009) Are Inositol Pyrophosphates Signalling Molecules? J CELL PHYSIOL , 220 (1) 8 - 15. 10.1002/jcp.21763.

Losito, O; Szijgyarto, Z; Resnick, AC; Saiardi, A; (2009) Inositol pyrophosphates and their unique metabolic complexity: analysis by gel electrophoresis. PLoS One , 4 (5) , Article e5580 . 10.1371/journal.pone.0005580. Green and gold open access
file

Onnebo, SM; Saiardi, A; (2009) Inositol pyrophosphates modulate hydrogen peroxide signalling. Biochem J , 423 (1) 109 - 118. 10.1042/BJ20090241.

2008

Draskovic, P; Saiardi, A; Bhandari, R; Burton, A; Ilc, G; Kovacevic, M; ... Podobnik, M; + view all (2008) Inositol hexakisphosphate kinase products contain diphosphate and triphosphate groups. CHEM BIOL , 15 (3) 274 - 286. 10.1016/j.chembiol.2008.01.011.

Marza, E; Long, T; Saiardi, A; Sumakovic, M; Eimer, S; Hall, DH; Lesa, GM; (2008) Polyunsaturated fatty acids influence synaptojanin localization to regulate synaptic vesicle recycling. Mol Biol Cell , 19 (3) 833 - 842. 10.1091/mbc.E07-07-0719.

Nagata, E; Saiardi, A; Snyder, SH; Takizawa, S; Takagi, S; (2008) The role of inositol hexakisphosphate kinases on central nerve system in the mammals. NEUROSCIENCE RESEARCH , 61 S39 - S39.

Resnick, AC; Saiardi, A; (2008) Inositol polyphosphate multikinase: metabolic architect of nuclear inositides. Front Biosci , 13 856 - 866.

Saiardi, A; Cockcroft, S; (2008) Human ITPK1: A Reversible Inositol Phosphate Kinase/Phosphatase That Links Receptor-Dependent Phospholipase C to Ca2+-Activated Chloride Channels (vol 1, art no er1, 2008). SCI SIGNAL , 1 (7) , Article er1.

Saiardi, A; Cockcroft, S; (2008) Human ITPK1: A Reversible Inositol Phosphate Kinase/Phosphatase That Links Receptor-Dependent Phospholipase C to Ca2+-Activated Chloride Channels. SCI SIGNAL , 1 (4) , Article pe5.

Tokuoka, SM; Saiardi, A; Nurrish, SJ; (2008) The mood stabilizer valproate inhibits both inositol- and diacylglycerol-signaling pathways in Caenorhabditis elegans. Mol Biol Cell , 19 (5) 2241 - 2250. 10.1091/mbc.E07-09-0982.

2007

Bhandari, R; Saiardi, A; Ahmadibeni, Y; Snowman, AM; Resnick, AC; Kristiansen, TZ; ... Snyder, SH; + view all (2007) Protein pyrophosphorylation by inositol pyrophosphates is a posttranslational event. P NATL ACAD SCI USA , 104 (39) 15305 - 15310. 10.1073/pnas.0707338104.

Illies, C; Gromada, J; Fiume, R; Leibiger, B; Yu, J; Juhl, K; ... Berggren, PO; + view all (2007) Requirement of inositol pyrophosphates for full exocytotic capacity in pancreatic beta cells. Science , 318 (5854) 1299 - 1302. 10.1126/science.1146824.

Onnebo, SM; Saiardi, A; (2007) Inositol pyrophosphates get the vip1 treatment. Cell , 129 (4) 647 - 649. 10.1016/j.cell.2007.05.002.

2006

Azevedo, C; Saiardi, A; (2006) Extraction and analysis of soluble inositol polyphosphates from yeast. Nat Protoc , 1 (5) 2416 - 2422. 10.1038/nprot.2006.337.

Bennett, M; Onnebo, SM; Azevedo, C; Saiardi, A; (2006) Inositol pyrophosphates: metabolism and signaling. Cell Mol Life Sci , 63 (5) 552 - 564. 10.1007/s00018-005-5446-z.

2005

Maffucci, T; Piccolo, E; Cumashi, A; Iezzi, M; Riley, AM; Saiardi, A; ... Falasca, M; + view all (2005) Inhibition of the phosphatidylinositol 3-kinase/Akt pathway by inositol pentakisphosphate results in antiangiogenic and antitumor effects. Cancer Res , 65 (18) 8339 - 8349. 10.1158/0008-5472.CAN-05-0121.

Nagata, E; Luo, HR; Saiardi, A; Bae, BI; Suzuki, N; Snyder, SH; (2005) Inositol hexakisphosphate kinase-2, a physiologic mediator of cell death. J Biol Chem , 280 (2) 1634 - 1640. 10.1074/jbc.M409416200. Gold open access

Resnick, AC; Snowman, AM; Kang, BN; Hurt, KJ; Snyder, SH; Saiardi, A; (2005) Inositol polyphosphate multikinase is a nuclear PI3-kinase with transcriptional regulatory activity. Proc Natl Acad Sci U S A , 102 (36) 12783 - 12788. 10.1073/pnas.0506184102.

Saiardi, A; Resnick, AC; Snowman, AM; Wendland, B; Snyder, SH; (2005) Inositol pyrophosphates regulate cell death and telomere length through phosphoinositide 3-kinase-related protein kinases. Proc Natl Acad Sci U S A , 102 (6) 1911 - 1914. 10.1073/pnas.0409322102.

2004

Kobayashi, M; Iaccarino, C; Saiardi, A; Heidt, V; Bozzi, Y; Picetti, R; ... Borrelli, E; + view all (2004) Simultaneous absence of dopamine D1 and D2 receptor-mediated signaling is lethal in mice. Proc Natl Acad Sci U S A , 101 (31) 11465 - 11470. 10.1073/pnas.0402028101.

Saiardi, A; Bhandari, R; Resnick, AC; Snowman, AM; Snyder, SH; (2004) Phosphorylation of proteins by inositol pyrophosphates. Science , 306 (5704) 2101 - 2105. 10.1126/science.1103344.

2003

Luo, HR; Huang, YE; Chen, JC; Saiardi, A; Iijima, M; Ye, K; ... Snyder, SH; + view all (2003) Inositol pyrophosphates mediate chemotaxis in Dictyostelium via pleckstrin homology domain-PtdIns(3,4,5)P3 interactions. Cell , 114 (5) 559 - 572.

2002

Caine, SB; Negus, SS; Mello, NK; Patel, S; Bristow, L; Kulagowski, J; ... Borrelli, E; + view all (2002) Role of dopamine D2-like receptors in cocaine self-administration: studies with D2 receptor mutant mice and novel D2 receptor antagonists. J Neurosci , 22 (7) 2977 - 2988.

Luo, HR; Saiardi, A; Yu, H; Nagata, E; Ye, K; Snyder, SH; (2002) Inositol pyrophosphates are required for DNA hyperrecombination in protein kinase c1 mutant yeast. Biochemistry , 41 (8) 2509 - 2515.

Saiardi, A; Sciambi, C; McCaffery, JM; Wendland, B; Snyder, SH; (2002) Inositol pyrophosphates regulate endocytic trafficking. Proc Natl Acad Sci U S A , 99 (22) 14206 - 14211. 10.1073/pnas.212527899.

2001

Luo, HR; Saiardi, A; Nagata, E; Ye, K; Yu, H; Jung, TS; ... Snyder, SH; + view all (2001) GRAB: a physiologic guanine nucleotide exchange factor for Rab3A, which interacts with inositol hexakisphosphate kinase. Neuron , 31 (3) 439 - 451.

Saiardi, A; Nagata, E; Luo, HR; Sawa, A; Luo, X; Snowman, AM; Snyder, SH; (2001) Mammalian inositol polyphosphate multikinase synthesizes inositol 1,4,5-trisphosphate and an inositol pyrophosphate. Proc Natl Acad Sci U S A , 98 (5) 2306 - 2311. 10.1073/pnas.041614598.

Saiardi, A; Nagata, E; Luo, HR; Snowman, AM; Snyder, SH; (2001) Identification and characterization of a novel inositol hexakisphosphate kinase. J Biol Chem , 276 (42) 39179 - 39185. 10.1074/jbc.M106842200. Gold open access

2000

Saiardi, A; Caffrey, JJ; Snyder, SH; Shears, SB; (2000) The inositol hexakisphosphate kinase family. Catalytic flexibility and function in yeast vacuole biogenesis. J Biol Chem , 275 (32) 24686 - 24692. 10.1074/jbc.M002750200. Gold open access

Saiardi, A; Caffrey, JJ; Snyder, SH; Shears, SB; (2000) Inositol polyphosphate multikinase (ArgRIII) determines nuclear mRNA export in Saccharomyces cerevisiae. FEBS Lett , 468 (1) 28 - 32.

1999

Saiardi, A; Erdjument-Bromage, H; Snowman, AM; Tempst, P; Snyder, SH; (1999) Synthesis of diphosphoinositol pentakisphosphate by a newly identified family of higher inositol polyphosphate kinases. Curr Biol , 9 (22) 1323 - 1326.

1998

Esposito, C; Miccadei, S; Saiardi, A; Civitareale, D; (1998) PAX 8 activates the enhancer of the human thyroperoxidase gene. Biochem J , 331 ( Pt 1) 37 - 40.

Huang, CF; Voglmaier, SM; Bembenek, ME; Saiardi, A; Snyder, SH; (1998) Identification and purification of diphosphoinositol pentakisphosphate kinase, which synthesizes the inositol pyrophosphate bis(diphospho)inositol tetrakisphosphate. Biochemistry , 37 (42) 14998 - 15004. 10.1021/bi981920l.

L'hirondel, M; Chéramy, A; Godeheu, G; Artaud, F; Saiardi, A; Borrelli, E; Glowinski, J; (1998) Lack of autoreceptor-mediated inhibitory control of dopamine release in striatal synaptosomes of D2 receptor-deficient mice. Brain Res , 792 (2) 253 - 262.

Saiardi, A; Abdel Samad, T; Picetti, R; Bozzi, Y; Baik, JH; Borrelli, E; (1998) The physiological role of dopamine D2 receptors. Adv Pharmacol , 42 521 - 524.

Saiardi, A; Borrelli, E; (1998) Absence of dopaminergic control on melanotrophs leads to Cushing's-like syndrome in mice. Mol Endocrinol , 12 (8) 1133 - 1139. 10.1210/mend.12.8.0144.

1997

Calabresi, P; Saiardi, A; Pisani, A; Baik, JH; Centonze, D; Mercuri, NB; ... Borrelli, E; + view all (1997) Abnormal synaptic plasticity in the striatum of mice lacking dopamine D2 receptors. J Neurosci , 17 (12) 4536 - 4544.

Maldonado, R; Saiardi, A; Valverde, O; Samad, TA; Roques, BP; Borrelli, E; (1997) Absence of opiate rewarding effects in mice lacking dopamine D2 receptors. Nature , 388 (6642) 586 - 589. 10.1038/41567.

Mercuri, NB; Saiardi, A; Bonci, A; Picetti, R; Calabresi, P; Bernardi, G; Borrelli, E; (1997) Loss of autoreceptor function in dopaminergic neurons from dopamine D2 receptor deficient mice. Neuroscience , 79 (2) 323 - 327.

Picetti, R; Saiardi, A; Abdel Samad, T; Bozzi, Y; Baik, JH; Borrelli, E; (1997) Dopamine D2 receptors in signal transduction and behavior. Crit Rev Neurobiol , 11 (2-3) 121 - 142.

Saiardi, A; Bozzi, Y; Baik, JH; Borrelli, E; (1997) Antiproliferative role of dopamine: loss of D2 receptors causes hormonal dysfunction and pituitary hyperplasia. Neuron , 19 (1) 115 - 126.

1995

Baik, JH; Picetti, R; Saiardi, A; Thiriet, G; Dierich, A; Depaulis, A; ... Borrelli, E; + view all (1995) Parkinsonian-like locomotor impairment in mice lacking dopamine D2 receptors. Nature , 377 (6548) 424 - 428. 10.1038/377424a0.

Saiardi, A; Falasca, P; Civitareale, D; (1995) Synergistic transcriptional activation of the thyrotropin receptor promoter by cyclic AMP-responsive-element-binding protein and thyroid transcription factor 1. Biochem J , 310 ( Pt 2) 491 - 496.

Saiardi, A; Tassi, V; De Filippis, V; Civitareale, D; (1995) Cloning and sequence analysis of human thyroid transcription factor 1. Biochim Biophys Acta , 1261 (2) 307 - 310.

1994

Civitareale, D; Saiardi, A; Falasca, P; (1994) Purification and characterization of thyroid transcription factor 2. Biochem J , 304 ( Pt 3) 981 - 985.

Saiardi, A; Falasca, P; Civitareale, D; (1994) The thyroid hormone inhibits the thyrotropin receptor promoter activity: evidence for a short loop regulation. Biochem Biophys Res Commun , 205 (1) 230 - 237. 10.1006/bbrc.1994.2654.

1993

Ceci, LR; Saiardi, A; Siculella, L; Quagliariello, C; (1993) A tRNA(Val) (GAC) gene of chloroplast origin in sunflower mitochondria is not transcribed. Plant Mol Biol , 23 (4) 727 - 736.

Civitareale, D; Castelli, MP; Falasca, P; Saiardi, A; (1993) Thyroid transcription factor 1 activates the promoter of the thyrotropin receptor gene. Mol Endocrinol , 7 (12) 1589 - 1595. 10.1210/mend.7.12.8145764.

1992

Saiardi, A; Quagliariello, C; (1992) RNA Editing of Cytochrome Oxidase Subunit III in Sunflower Mitochondria. Plant Physiol , 98 (4) 1261 - 1263.

1990

Quagliariello, C; Saiardi, A; Gallerani, R; (1990) The cytochrome oxidase subunit III gene in sunflower mitochondria is cotranscribed with an open reading frame conserved in higher plants. Curr Genet , 18 (4) 355 - 363.

This list was generated on Thu Jul 24 12:57:42 2014 BST.