Glutamate‐induced octamer DNA binding and transcriptional control in cultured radial glia cells

Abstract

Glutamate, the main excitatory neurotransmitter in the vertebrate brain, is critically involved in gene expression regulation in neurons and in glia cells. Neuron-glia interactions provide the framework for synaptic plasticity. Retinal and cerebellar radial glia cells surround glutamatergic excitatory synapses and sense synaptic activity through glutamate receptors expressed in their membranes. Several glutamatedependent membrane to nuclei signaling cascades have been described in these cells. Octamer DNA binding factors, namely Oct-1 and Oct-2 recognize similar DNA sequences on regulatory regions, but their final transcriptional effect depends on several factors. By these means, different responses can be achieved in different cell types. Here, we describe a comparison between the glutamate-induced DNA binding of octamer factors and their functional activities in two important types of radial glia, retinal Mü ller and cerebellar Bergmann glial cells. While Oct-1 is expressed in both cell types and in both glutamate treatments results in an increase in Oct-1 DNA binding, this complex is capable of transactivating a reporter gene only in Mü ller glia cells. In contrast, Oct-2 expression is restricted to Bergmann glia cells in which glutamate treatment results in an augmentation of Oct-2 DNA binding complexes and the repression of kainate binding protein gene transcription. Our present findings demonstrate a differential role for Oct-1 and Oct-2 transcription factors in glial glutamate signaling, and further strengthen the notion of an important role for glial cells in glutamatergic transactions in the central nervous system.

Sigma receptors [σRs]: biology in normal and diseased states

“…Neurons are not the only cell type in the nervous system to be damaged by high concentrations of Glu ( 914 ). Functional NMDAR recently have been reported in brain glia ( 915 ), astrocytes ( 247 , 916 ) and oligodendroglia ( 409 , 559 , 917 ,). Glial and neuronal NMDARs are functionally and structurally different from the neuronal NMDR; however, the structure of σRs in these cell types is not known at present, and it can only be speculated that the alteration of σRs in these cell types would ameliorate damage caused by overstimulation of NMDARs.…”

Glutamate Transporter-Dependent mTOR Phosphorylation in Müller Glia Cells

“…Glu stimulation has been linked to transcriptional control in glial cells (Lopez-Bayghen et al, 2006). Following the demonstration of GLAST-induced Ca 2+ -dependent activation of the translation regulator mTOR, the possible induction of gene transcription by this process was analysed.…”

“…The functional significance of signalling through the transporters compared with the cascades activated via Glu receptors, and the fact that both would lead to gene expression regulation in glia cells (Lopez-Bayghen et al, 2006), is elusive at this point. Yet, it is conceivable that the difference in the kinetics of activation, favoured by lower affinity of the transporters and their higher density (Danbolt, 2001), is the basis for a transporter-selective response at the level of transcriptional and/or translational control.…”

“…Also along this line, the activation of Glu receptors in Müller cells feeds back on to neurons by triggering the release of neuroactive compounds (Uchihori and Puro, 1993; Lopez-Colome et al, 1995; Lopez et al, 1998; Lopez-Bayghen et al, 2006). …”

Untitled

“…Thus, there is a significant enrichment in upstream and intronic MCEs but not in MCEs downstream of presynaptic genes. Several of these transcription factors are known to be involved in synaptogenesis or neuronal function such as Crx [35], Lh3x [36], GR[37,38], SMAD [39,40], and OCT-1 [41]. Interestingly, of the 16 enriched TFBSs, 11 (CRX, FOXP3, GR, HOXA4, LHX3, NKX3A, POU6F1, RFX1, S8, SMAD, and TTF1) were located within duplicated MCEs discussed above.…”