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NRGN  -  neurogranin (protein kinase C substrate, RC3)

Homo sapiens

Synonyms: Neurogranin, Ng, RC3, hng
 
 
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Disease relevance of NRGN

  • In the model, knockout of neurogranin strongly diminishes the LTP induced by a single 100 Hz, 1 s tetanus and slightly enhances LTD, in accord with experimental data [1].
  • One of the largest gene classes identified in this screen includes several neuroendocrine-associated genes (neuron-specific enolase, neurogranin), suggesting that EGR1 overexpression may contribute to the neuroendocrine differentiation that often accompanies prostate cancer progression [2].
  • Outer membranes (OMs) were prepared from the Neisseria meningitidis (Nm) strain 44/76, N. gonorrhoeae (Ng) NRL 8658, and N. lactamica (N1) ATCC 23970 [3].
 

Psychiatry related information on NRGN

  • The RC scales were as internally consistent as the clinical scales and correlated strongly with their original counterparts (except for RC3/Hysteria) [4].
 

High impact information on NRGN

  • We show that ectopic expression of RC3 in IL-2-dependent T cells increases the intracellular Ca(2+) concentration and induces apoptosis even in the presence of cytokine [5].
  • Buffering the Ca(2+) increase with the cytoplasmic Ca(2+) chelator BAPTA-AM [1,2-bis(2-aminophenoxy)ethane-N,N,N1,N-tetraacetic acid] blocks RC3-induced apoptosis, indicating that the rise in intracellular Ca(2+) is required for apoptotic death [5].
  • Transcriptional program of apoptosis induction following interleukin 2 deprivation: identification of RC3, a calcium/calmodulin binding protein, as a novel proapoptotic factor [5].
  • Quantitative reverse transcription-polymerase chain reaction (PCR) confirmed the highest frequency of mt-derived transcripts, along with the mRNAs for neurogranin (NGN, a protein kinase C substrate) and the complement lysis inhibitor clusterin among the top 5 most abundant transcripts [6].
  • HIKE motifs occur also in gelsolin, neurogranin, neuromodulin and in the PH domain of Bruton tyrosin kinase (BTK) [7].
 

Biological context of NRGN

  • The human NRGN gene spans approximately 12 kb and contains four exons and three introns [8].
  • RC3 mutants unable to bind calmodulin fail to increase intracellular Ca(2+) levels and to induce apoptosis [5].
  • Surprisingly, one gene whose transcription substantially increased was RC3 (also called neurogranin), which encodes a calmodulin binding protein thought to be a neural-specific factor involved in learning and memory [5].
  • Role of the neurogranin concentrated in spines in the induction of long-term potentiation [1].
  • We also searched for additional proteins that might interact with neurogranin by screening brain cDNA libraries [9].
 

Anatomical context of NRGN

 

Associations of NRGN with chemical compounds

  • The data reported in this work suggest that NRGN is a direct target of thyroid hormone in human brain, and that control of expression of this gene could underlay many of the consequences ofhypothyroidism on mental states during development as well as in adult subjects [12].
  • In contrast to T3, neither retinoic acid nor dexamethasone influences neurogranin expression despite the presence of respective functional receptors [11].
  • Depending on the rate at which the NRGNP color changes, reduced glutathione (slow) is readily distinguishable from oxidized glutathione (no aggregation and no displacement) and from cysteine and homocysteine (fast) [13].
  • Analysis of neurogranin mRNA, a marker of hippocampal neurons, with in situ hybridization revealed a dramatic and selective loss of CA1 neurons in the placebo-treated ovariectomized gerbils, whereas both 0.5 mg and 1 mg pellets of 17beta-estradiol prevented cell loss [14].
  • The binding affinity of a protein kinase C substrate, neurogranin peptide NG(28-43), to a sodium dodecyl sulfate micelle was analyzed quantitatively by the diffusion coefficient (Da) of the peptide determined by pulsed field gradient NMR [15].
 

Other interactions of NRGN

  • The concentration of calmodulin in neurons is considerably less than the total concentration of the apocalmodulin-binding proteins neurogranin and GAP-43, resulting in a low level of free calmodulin in the resting state [1].
  • The effect of lipid moieties on activation of conventional (PKC-alpha and -beta1), novel (PKC-delta) and atypical (PKC-zeta) PKC isoforms was evaluated in an in vitro assay, using biotinylated neurogranin as a substrate [16].
  • The expression of several region-specific genes - neurogenic differentiation 1 (cerebellum), cocaine- and amphetamine-regulated transcript (thalamus), and neurogranin (white matter) - was confirmed using quantitative fluorescent real-time RT-PCR [17].
 

Analytical, diagnostic and therapeutic context of NRGN

References

  1. Role of the neurogranin concentrated in spines in the induction of long-term potentiation. Zhabotinsky, A.M., Camp, R.N., Epstein, I.R., Lisman, J.E. J. Neurosci. (2006) [Pubmed]
  2. EGR1 target genes in prostate carcinoma cells identified by microarray analysis. Svaren, J., Ehrig, T., Abdulkadir, S.A., Ehrengruber, M.U., Watson, M.A., Milbrandt, J. J. Biol. Chem. (2000) [Pubmed]
  3. Serum antibodies to cross-reactive Neisseria outer membrane antigens in healthy persons and patients with meningococcal disease. Maeland, J.A., Wedege, E. APMIS (1989) [Pubmed]
  4. Psychometric evaluation of the restructured clinical scales of the MMPI-2. Simms, L.J., Casillas, A., Clark, L.A., Watson, D., Doebbeling, B.N. Psychological assessment. (2005) [Pubmed]
  5. Transcriptional program of apoptosis induction following interleukin 2 deprivation: identification of RC3, a calcium/calmodulin binding protein, as a novel proapoptotic factor. Devireddy, L.R., Green, M.R. Mol. Cell. Biol. (2003) [Pubmed]
  6. Transcript profiling of human platelets using microarray and serial analysis of gene expression. Gnatenko, D.V., Dunn, J.J., McCorkle, S.R., Weissmann, D., Perrotta, P.L., Bahou, W.F. Blood (2003) [Pubmed]
  7. Large and diverse numbers of human diseases with HIKE mutations. Ciccarelli, F.D., Acciarito, A., Alberti, S. Hum. Mol. Genet. (2000) [Pubmed]
  8. Structure, organization, and chromosomal mapping of the human neurogranin gene (NRGN). Martínez de Arrieta, C., Pérez Jurado, L., Bernal, J., Coloma, A. Genomics (1997) [Pubmed]
  9. Interactions between neurogranin and calmodulin in vivo. Prichard, L., Deloulme, J.C., Storm, D.R. J. Biol. Chem. (1999) [Pubmed]
  10. Localization of RC3 (neurogranin) in rat brain subcellular fractions. Watson, J.B., Szijan, I., Coulter, P.M. Brain Res. Mol. Brain Res. (1994) [Pubmed]
  11. Thyroid hormone-regulated expression of RC3/neurogranin in the immortalized hypothalamic cell line GT1-7. Morte, B., Iñiguez, M.A., Lorenzo, P.I., Bernal, J. J. Neurochem. (1997) [Pubmed]
  12. The human RC3 gene homolog, NRGN contains a thyroid hormone-responsive element located in the first intron. Martínez de Arrieta, C., Morte, B., Coloma, A., Bernal, J. Endocrinology (1999) [Pubmed]
  13. Nile red-adsorbed gold nanoparticles for selective determination of thiols based on energy transfer and aggregation. Chen, S.J., Chang, H.T. Anal. Chem. (2004) [Pubmed]
  14. Estrogen prevents the loss of CA1 hippocampal neurons in gerbils after ischemic injury. Shughrue, P.J., Merchenthaler, I. Neuroscience (2003) [Pubmed]
  15. Determination of the binding constant of a protein kinase C substrate, NG(28-43), to sodium dodecyl sulfate via the diffusion coefficient measured by pulsed field gradient nuclear magnetic resonance. Chien, W.J., Cheng, S.F., Chang, D.K. Anal. Biochem. (1998) [Pubmed]
  16. Fatty acid and phorbol ester-mediated interference of mitogenic signaling via novel protein kinase C isoforms in pancreatic beta-cells (INS-1). Wrede, C.E., Dickson, L.M., Lingohr, M.K., Briaud, I., Rhodes, C.J. J. Mol. Endocrinol. (2003) [Pubmed]
  17. A database for regional gene expression in the human brain. Siu, I.M., Lal, A., Riggins, G.J. Brain Res. Gene Expr. Patterns (2001) [Pubmed]
  18. Conformation of a protein kinase C substrate NG(28-43), and its analog in aqueous and sodium dodecyl sulfate micelle solutions. Chang, D.K., Chien, W.J., Arunkumar, A.I. Biophys. J. (1997) [Pubmed]
  19. Evidence of altered neurogranin immunoreactivity in areas 9 and 32 of schizophrenic prefrontal cortex. Broadbelt, K., Ramprasaud, A., Jones, L.B. Schizophr. Res. (2006) [Pubmed]
  20. RC3/neurogranin is expressed in pyramidal neurons of motor and somatosensory cortex in normal and denervated monkeys. Guadaño-Ferraz, A., Viñuela, A., Oeding, G., Bernal, J., Rausell, E. J. Comp. Neurol. (2005) [Pubmed]
 
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