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Neurochem Res (2008) 33:14421451 DOI 10.1007/s11064-007-9572-x
ORIGINAL PAPER
Serum Differentially Modies the Transcription and Translation of NMDAR Subunits in Retinal Neurons
Irene Lee-Rivera Edith Lpez J. Prisco Palma Ana Mara Lpez-Colom
Accepted: 12 December 2007 / Published online: 13 February 2008 Springer Science+Business Media, LLC 2008
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-specic 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 modied 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 ndings 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.
Keywords Glutamate Retina Growth factors NMDAR composition
Introduction
Glutamate (L-Glu) is the excitatory neurotransmitter at the main signaling pathway of the vertebrate retina [1]. N-methyl-D-aspartate receptors (NMDAR), one of the major subtypes of ionotropic glutamate receptors, play an important role in retinal synaptic transmission, particularly at the inner plexiform layer [2]. The NMDARs are calcium-permeable tetrameric ligand-gated channels [3], assembled by NR1, NR2 (AD), and in some cases NR3 subunits [4]. The functional diversity of NMDARs resides in the differential assembly of subunits [5]. The NR1 subunit is essential for the formation of the ion channel, and contains the glycine coagonist-binding site. The NR2 subunits modulate channel properties, including peak open probability, sensitivity to glutamate, and response kinetics. NMDARs in vivo have been shown to include, in addition to NR1 subunits, one or more NR2 subunit types and/or NR3 subunits [6, 7].
Eight functional variants derived from the alternative splicing of NR1 pre-mRNA have been described, which arise from the insertion or deletion...