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Serum Differentially Modifies the Transcription and Translation of NMDAR Subunits in Retinal Neurons

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Abstract

The N-methyl-d-Aspartate type of glutamate receptor (NMDAR) plays a major role in the vertebrate retina. Expression of NR1 splice-variants and NR2 subunits in the retina differs from that in the brain, suggesting a tissue-specific heteromeric assembly of NMDARs. We previously demonstrated that serum alters retinal glutamate receptor properties. In order to relate this effect to NMDAR subunit composition, we here studied the effect of serum on the expression of NMDAR subunits and splice-variants in chick retinal neurons in primary culture. Our results show that mRNA and protein expression of NR1 alternative splice-variants and NR2 subunits are differentially modified by glutamate contained in serum. Such alteration suggests that NMDAR structure is reversed to embryonic heteromeric composition, through the control of subunit availability. The present findings could be relevant for the understanding of the lack of effect in the retina, of drugs which have been shown to protect cortical neurons from glutamate-induced excitotoxicity in those pathological or clinical conditions in which the retina is exposed to serum.

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References

  1. Massey SC, Miller RF (1990) N-methyl-D-aspartate receptors of ganglion cells in rabbit retina. J Neurophysiol 63:16–30

    PubMed  CAS  Google Scholar 

  2. Fletcher EL, Hack I, Brandstäter JH et al (2000) Synaptic localization of NMDA receptor subunits in the rat retina. J Comp Neurol. 420:98–112

    Article  PubMed  CAS  Google Scholar 

  3. Dingledine R, Borges K, Bowie D et al (1999) The glutamate receptor ion channels. Pharmacol Rev 51:7–61

    PubMed  CAS  Google Scholar 

  4. Hollmann M, Heinemann S (1994) Cloned glutamate receptors. Annu Rev Neurosci 17:31–108

    Article  PubMed  CAS  Google Scholar 

  5. Mori H, Mishina M (1995) Structure and function of the NMDA receptor channel. Neuropharmacology 34:1219–1237

    Article  PubMed  CAS  Google Scholar 

  6. Monyer H, Sprengel R, Schoepfer R et al (1992) Heteromeric NMDA receptors: molecular and functional distinction of subtypes. Science 256:1217–1221

    Article  PubMed  CAS  Google Scholar 

  7. Das S, Sasaki YF, Rothe T et al (1998) Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3A. Nature 393:377–381

    Article  PubMed  CAS  Google Scholar 

  8. Zukin RS, Bennett MV (1995) Alternatively spliced isoforms of the NMDAR1 receptor subunit. Trends Neurosci 18:306–313

    Article  PubMed  CAS  Google Scholar 

  9. Ehlers MD, Zhang S, Bernhardt JP et al (1996) Inactivation of NMDA receptors by direct interaction of calmodulin with the NR1 subunit. Cell 84:745–755

    Article  PubMed  CAS  Google Scholar 

  10. Ehlers MD, Fung ET, O’Brien RJ et al (1998). Splice variant-specific interaction of the NMDA receptor subunit NR1 with neuronal intermediate filaments. J Neurosci 18:720–730

    PubMed  CAS  Google Scholar 

  11. Okabe S, Miwa A, Okado H (1999) Alternative splicing of the C-terminal domain regulates cell surface expression of the NMDA receptor NR1 subunit. J Neurosci 19:7781–7792

    PubMed  CAS  Google Scholar 

  12. Standley S, Roche KW, McCallum J et al (2000) PDZ domain supression of an ER retention signal in NMDA receptor NR1 splice variants. Neuron 28:887–898

    Article  PubMed  CAS  Google Scholar 

  13. Brandstäter JH, Hartveit E, Sassoe-Pognetto M et al (1994) Expression of NMDA and high-affinity kainate receptor subunit mRNAs in the adult rat retina. Eur J Neurosci 6:1100–1112

    Article  Google Scholar 

  14. Gründer T, Kohler K, Kaletta A et al (2000) The distribution and developmental regulation of NMDA receptor subunit proteins in the outer and inner retina of the rat. J Neurobiol 44:333–342

    Article  PubMed  Google Scholar 

  15. Brandstätter JH, Koulen P, Wässle H (1998) Diversity of glutamate receptors in the mammalian retina. Vision Res 38:1385–1397

    Article  PubMed  Google Scholar 

  16. Cull-Candy S, Brickley S, Farrant M (2001) NMDA receptor subunits: diversity, development and disease. Curr Opin Neurobiol 11:327–335

    Article  PubMed  CAS  Google Scholar 

  17. Lee-Rivera I, Zarain-Herzberg A, López-Colomé AM (2003) Developmental expression of N-methyl-D-aspartate glutamate receptor 1 splice variants in the chick retina. J Neurosci Res 73:369–383

    Article  PubMed  CAS  Google Scholar 

  18. Kreutz MR, Bockers TM, Bockmann J et al (1998) Axonal injury alters alternative splicing of the retinal NR1 receptor: the preferential expression of the NR1b isoforms is crucial for retinal ganglion cell survival. J Neurosci 18:8278–8291

    PubMed  CAS  Google Scholar 

  19. Bai G, Kusiak JW (1997) Nerve growth factor up-regulates the N-methyl-D-aspartate receptor subunit 1 promoter in PC12 cells. J Biol Chem 272:5936–5942

    Article  PubMed  CAS  Google Scholar 

  20. Sonntag W, Bennett S, Khan A et al (2000) Age and insulin-like growth factor-1 modulate N-methyl-D-aspartate receptor subtype expression in rats. Brain Res Bull 51:331–338

    Article  PubMed  CAS  Google Scholar 

  21. Kido N, Tanihara H, Honjo M et al (2000). Neuroprotective effects of brain-derived neurotrophic factor in eyes with NMDA-induced neuronal death. Brain Res 884:59–67

    Article  PubMed  CAS  Google Scholar 

  22. Suen P, Wu K, Levine E et al (1997) Brain-derived neurotrophic factor rapidly enhances phosphorylation of the postsynaptic N-methyl-D-aspartate receptor subunit 1. Proc Natl Acad Sci USA 94:8191–8195

    Article  PubMed  CAS  Google Scholar 

  23. Lin S, Wu K, Levine E et al (1998) BDNF acutely increases tyrosine phosphorylation of the NMDA receptor subunit 2B in cortical and hippocampal postsynaptic densities. Brain Res Mol Brain Res 55:20–27

    Article  PubMed  CAS  Google Scholar 

  24. Glazner G, Mattson M (2000) Differential effects of BDNF, ADNF9, and TNFalpha on levels of NMDA receptor subunits, calcium homeostasis, and neuronal vulnerability to excitotoxicity. Exp Neurol 161:442–452

    Article  PubMed  CAS  Google Scholar 

  25. López-Colomé AM, Romo-de-Vivar M (1996) Serum affects the characteristics of excitatory amino acid-binding sites on Muller cells. Neurosci Res 25:25–32

    Article  PubMed  Google Scholar 

  26. López-Colomé AM, Somohano F (1984) Localization of L-glutamate and L-aspartate synaptic receptors in chick retinal neurons. Brain Res 298:159–162

    Article  PubMed  Google Scholar 

  27. Zarain-Herzberg A, Lee-Rivera I, Rodríguez G et al (2005) Cloning and characterization of the chick NMDA receptor subunit-1 gene. Brain Res Mol Brain Res 137:235–251

    Article  PubMed  CAS  Google Scholar 

  28. Lamas M, Lee-Rivera I, López-Colomé AM (2005) Cell-specific expression of N-methyl-D-aspartate receptor subunits in Müller glia and neurons from the chick retina. Invest Ophthalmol Vis Sci 46:3570–3577

    Article  PubMed  Google Scholar 

  29. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    Article  PubMed  CAS  Google Scholar 

  30. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  PubMed  CAS  Google Scholar 

  31. Liu SJ, Kaczmarek LK (1998) The expression of two splice variants of the Kv3.1 potassium channel gene is regulated by different signaling pathways. J Neurosci 18:2881–2890

    PubMed  CAS  Google Scholar 

  32. Akopian AN, Okuse K, Souslova V et al (1999) Trans-splicing of a voltage-gated sodium channel is regulated by nerve growth factor. FEBS Lett 445:177–182

    Article  PubMed  CAS  Google Scholar 

  33. Wollmuth LP, Sobolevsky AI (2004) Structure and gating of the glutamate receptor ion channel. Trends Neurosci 27:321–328

    Article  PubMed  CAS  Google Scholar 

  34. Durand GM, Bennett MV, Zukin RS (1993) Splice variants of the N-methyl-D-aspartate receptor NR1 identify domains involved in regulation by polyamines and protein kinase C. Proc Natl Acad Sci USA 90:6731–6735

    Article  PubMed  CAS  Google Scholar 

  35. Hollmann M, Boulter J, Maron C et al (1993) Zinc potentiates agonist-induced currents at certain splice variants of the NMDA receptor. Neuron 10:943–954

    Article  PubMed  CAS  Google Scholar 

  36. Lombardi G, Moroni F (1994) Glutamate receptor antagonists protect against ischemia induced retinal damage. Dev Neurosci 25:293–300

    Google Scholar 

  37. Castillo J, Davalos A, Noya M (1997) Progression of ischaemic stroke and excitotoxic aminoacids. Lancet 349:79–83

    Article  PubMed  CAS  Google Scholar 

  38. Kutsuwada T, Kashiwabuchi N, Mori H et al (1992) Molecular diversity of the NMDA receptor channel. Nature 358:36–41

    Article  PubMed  CAS  Google Scholar 

  39. Monyer H, Burnashev N, Laurie DJ et al (1994) Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 12:529–540

    Article  PubMed  CAS  Google Scholar 

  40. Prybylowski K, Wenthold RJ (2004) N-Methyl-D-aspartate receptors: subunit assembly and trafficking to the synapse. J Biol Chem 279:9673–9676

    Article  PubMed  CAS  Google Scholar 

  41. Abe M, Fukaya M, Yagi T, Mishina M et al (2004) NMDA receptor GluRepsilon/NR2 subunits are essential for postsynaptic localization and protein stability of GluRzeta1/NR1 subunit. J Neurosci 24:7292–7304

    Article  PubMed  CAS  Google Scholar 

  42. Groc L, Heine M, Cousins SL, Stephenson FA et al (2006) NMDA receptor surface mobility depends on NR2A-2B subunits. Proc Natl Acad Sci USA 103(49):18769–18774

    Article  PubMed  CAS  Google Scholar 

  43. Tyszkiewicz JP, Gu Z, Wang X, Cai X, Yan Z (2004) Group II metabotropic glutamate receptors enhance NMDA receptor currents via a protein kinase C-dependent mechanism in pyramidal neurones of rat prefrontal cortex. J Physiol 554(Pt 3):765–777

    PubMed  CAS  Google Scholar 

  44. Hardingham GE, Fukunaga Y, Bading H (2002) Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways. Nat Neurosci 5:405–414

    PubMed  CAS  Google Scholar 

  45. Bittigau P, Ikonomidou C (1997) Glutamate in neurologic diseases. J Child Neurol 12:471–485

    Article  PubMed  CAS  Google Scholar 

  46. Resink A, Villa M, Benke D et al (1995) Regulation of the expression of NMDA receptor subunits in rat cerebellar granule cells: effect of chronic K(+)-induced depolarization and NMDA exposure. J Neurochem 64:558–565

    Article  PubMed  CAS  Google Scholar 

  47. Chew LJ, Gallo V (1998) Regulation of ion channel expression in neural cells by hormones and growth factors. Mol Neurobiol 18:175–225

    Article  PubMed  CAS  Google Scholar 

  48. Wood MW, VanDongen HM, VanDongen AM (1996) The 5’-untranslated region of the N-methyl-D-aspartate receptor NR2A subunit controls efficiency of translation. J Biol Chem 271:8115–8120

    Article  PubMed  CAS  Google Scholar 

  49. VanDongen AM, VanDongen HM (2004) Effects of mRNA untranslated regions on translational efficiency of NMDA receptor subunits. Neurosignals 13:194–206

    Article  PubMed  CAS  Google Scholar 

  50. Isenmann S, Kretz A, Cellerino A (2003) Molecular determinants of retinal ganglion cell development, survival, and regeneration. Prog Retin Eye Res 22:483–543

    Article  PubMed  CAS  Google Scholar 

  51. Scheetz AJ, Constantine-Paton M (1994) Modulation of NMDA receptor function: implications for vertebrate neural development. FASEB J 745–752

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Acknowledgments

This work was partially supported by grants 42640-Q from CONACYT and IN203507 from PAPIIT/UNAM to A.M.L.-C.

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Authors and Affiliations

  1. Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apartado Postal 70-253, Ciudad Universitaria, Mexico, DF, 04510, Mexico

    Irene Lee-Rivera, Edith López, J. Prisco Palma & Ana María López-Colomé

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  1. Irene Lee-Rivera
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  2. Edith López
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  3. J. Prisco Palma
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  4. Ana María López-Colomé
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Correspondence to Ana María López-Colomé.

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Special issue article in honor of Dr. Ricardo Tapia.

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Lee-Rivera, I., López, E., Palma, J.P. et al. Serum Differentially Modifies the Transcription and Translation of NMDAR Subunits in Retinal Neurons. Neurochem Res 33, 1442–1451 (2008). https://doi.org/10.1007/s11064-007-9572-x

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  • DOI: https://doi.org/10.1007/s11064-007-9572-x

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