? The long term goal of this application over the past 30 years has been to? elueidate molecular signaling systems in the brain whieh may be relevant to? aetions of psyehotropic drugs. We propose continuing a characterization of? multiple systems but with a special foeus on three: D-serine, neuronal nitric? oxide synthase (nNOS) associated proteins, and higher inositol polyphosphates.? (1) D-serine: We will extend our evidence for D-serine as a neuromodulator? serving as the endogenous ligand for NMDA-glutamate receptors. We will? eharaeterize serine racemase, the enzyme we have recently purified and cloned,? which converts L- to D-serine. We will develop knockouts and transgenics for? serine racemase and d-amino aeid oxidase, the enzyme which appears to? physiologically degrade D-serine. (2) nNOS Associated Proteins-Focus on CAPON:? CAPON is a nNOS associated protein we discovered, which may serve as a scaffold? linking nNOS to other proteins. We recently discovered interactions of CAPON? with synapsin, a synaptie vesicle protein, and Dexrasl, a new member of the Ras? family. We will continue our studies implicating CAPON as a bridge delivering? NO formed by nNOS to synapsin to affect synaptic vesiele funetion, and to? Dexrasl to influenee its downstream signaling to alter nuelear funetion. (3)? Higher Inositol Polyphosphates: Higher inositol polyphosphates are? pyrophosphates with e about :-rgetic phosphate groups that we think may mediate? phosphate transfer to proteins, perhaps assoeiated with synaptic vesicle? turnover. We will extend our studies in which we purified and cloned IP 6? kinase, which forms the pyrophosphate PP-IPs (IP7 ). We will characterize? functions of this enzyme and a related protein, PiUS that also possesses IP6? kinase activity. We will characterize putative protein phosphorylation by PP-IP? 5. We will also complete purif aboutcation and cloning of PP-IPs kinase which? forms bis PP-IP4, which contains two pyrophosphate groups.
| Fu, Chenglai; Tyagi, Richa; Chin, Alfred C et al. (2018) Inositol Polyphosphate Multikinase Inhibits Angiogenesis via Inositol Pentakisphosphate-Induced HIF-1? Degradation. Circ Res 122:457-472 |
| Kornberg, Michael D; Bhargava, Pavan; Kim, Paul M et al. (2018) Dimethyl fumarate targets GAPDH and aerobic glycolysis to modulate immunity. Science 360:449-453 |
| Sbodio, Juan I; Snyder, Solomon H; Paul, Bindu D (2018) Golgi stress response reprograms cysteine metabolism to confer cytoprotection in Huntington's disease. Proc Natl Acad Sci U S A 115:780-785 |
| Paul, Bindu D; Snyder, Solomon H (2018) Gasotransmitter hydrogen sulfide signaling in neuronal health and disease. Biochem Pharmacol 149:101-109 |
| Peng, Ying-Jie; Zhang, Xiuli; Gridina, Anna et al. (2017) Complementary roles of gasotransmitters CO and H2S in sleep apnea. Proc Natl Acad Sci U S A 114:1413-1418 |
| Sbodio, Juan I; Snyder, Solomon H; Paul, Bindu D (2016) Transcriptional control of amino acid homeostasis is disrupted in Huntington's disease. Proc Natl Acad Sci U S A 113:8843-8 |
| Kim, Hyo Jung; Cha, Jiyoung Y; Seok, Jo Woon et al. (2016) Dexras1 links glucocorticoids to insulin-like growth factor-1 signaling in adipogenesis. Sci Rep 6:28648 |
| Choi, Hyong Woo; Tian, Miaoying; Manohar, Murli et al. (2015) Human GAPDH Is a Target of Aspirin's Primary Metabolite Salicylic Acid and Its Derivatives. PLoS One 10:e0143447 |
| Paul, Bindu D; Snyder, Solomon H (2015) H2S: A Novel Gasotransmitter that Signals by Sulfhydration. Trends Biochem Sci 40:687-700 |
| Ahmed, Ishrat; Sbodio, Juan I; Harraz, Maged M et al. (2015) Huntington's disease: Neural dysfunction linked to inositol polyphosphate multikinase. Proc Natl Acad Sci U S A 112:9751-6 |
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