Role of Satb1 and Satb2 Transcription Factors in the Glutamate Receptors Expression and Ca<sup>2+</sup> Signaling in the Cortical Neurons In Vitro
Transcription factors Satb1 and Satb2 are involved in the processes of cortex development and maturation of neurons. Alterations in the expression of their target genes can lead to neurodegenerative processes. Molecular and cellular mechanisms of regulation of neurotransmission by these transcriptio...
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2021-05-01
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| Series: | International Journal of Molecular Sciences |
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| author | Egor A. Turovsky Maria V. Turovskaya Evgeniya I. Fedotova Alexey A. Babaev Victor S. Tarabykin Elena G. Varlamova |
| author_facet | Egor A. Turovsky Maria V. Turovskaya Evgeniya I. Fedotova Alexey A. Babaev Victor S. Tarabykin Elena G. Varlamova |
| author_sort | Egor A. Turovsky |
| collection | DOAJ |
| description | Transcription factors Satb1 and Satb2 are involved in the processes of cortex development and maturation of neurons. Alterations in the expression of their target genes can lead to neurodegenerative processes. Molecular and cellular mechanisms of regulation of neurotransmission by these transcription factors remain poorly understood. In this study, we have shown that transcription factors Satb1 and Satb2 participate in the regulation of genes encoding the NMDA-, AMPA-, and KA- receptor subunits and the inhibitory GABA(A) receptor. Deletion of gene for either Satb1 or Satb2 homologous factors induces the expression of genes encoding the NMDA receptor subunits, thereby leading to higher amplitudes of Ca<sup>2+</sup>-signals in neurons derived from the Satb1-deficient (Satb1<sup>fl/+</sup> * Nex<sup>Cre/+</sup>) and Satb1-null mice (Satb1<sup>fl/fl</sup> * Nex<sup>Cre/+</sup>) in response to the selective agonist reducing the EC50 for the NMDA receptor. Simultaneously, there is an increase in the expression of the <i>Gria2</i> gene, encoding the AMPA receptor subunit, thus decreasing the Ca<sup>2+</sup>-signals of neurons in response to the treatment with a selective agonist (5-Fluorowillardiine (FW)). The Satb1 deletion increases the sensitivity of the KA receptor to the agonist (domoic acid), in the cortical neurons of the Satb1-deficient mice but decreases it in the Satb1-null mice. At the same time, the Satb2 deletion decreases Ca<sup>2+</sup>-signals and the sensitivity of the KA receptor to the agonist in neurons from the Satb1-null and the Satb1-deficient mice. The Satb1 deletion affects the development of the inhibitory system of neurotransmission resulting in the suppression of the neuron maturation process and switching the GABAergic responses from excitatory to inhibitory, while the Satb2 deletion has a similar effect only in the Satb1-null mice. We show that the Satb1 and Satb2 transcription factors are involved in the regulation of the transmission of excitatory signals and inhibition of the neuronal network in the cortical cell culture. |
| first_indexed | 2024-03-10T10:49:57Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:49:57Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-988290a7aa534713a3a0dbf405ac9f232023-11-21T22:20:49ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012211596810.3390/ijms22115968Role of Satb1 and Satb2 Transcription Factors in the Glutamate Receptors Expression and Ca<sup>2+</sup> Signaling in the Cortical Neurons In VitroEgor A. Turovsky0Maria V. Turovskaya1Evgeniya I. Fedotova2Alexey A. Babaev3Victor S. Tarabykin4Elena G. Varlamova5Federal Research Center “Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences”, Institute of Cell Biophysics of the Russian Academy of Sciences, 142290 Pushchino, RussiaFederal Research Center “Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences”, Institute of Cell Biophysics of the Russian Academy of Sciences, 142290 Pushchino, RussiaFederal Research Center “Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences”, Institute of Cell Biophysics of the Russian Academy of Sciences, 142290 Pushchino, RussiaInstitute of Neuroscience, Lobachevsky State University of Nizhniy Novgorod, 23 Prospekt Gagarina, 603950 Nizhny Novgorod, RussiaInstitute of Neuroscience, Lobachevsky State University of Nizhniy Novgorod, 23 Prospekt Gagarina, 603950 Nizhny Novgorod, RussiaFederal Research Center “Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences”, Institute of Cell Biophysics of the Russian Academy of Sciences, 142290 Pushchino, RussiaTranscription factors Satb1 and Satb2 are involved in the processes of cortex development and maturation of neurons. Alterations in the expression of their target genes can lead to neurodegenerative processes. Molecular and cellular mechanisms of regulation of neurotransmission by these transcription factors remain poorly understood. In this study, we have shown that transcription factors Satb1 and Satb2 participate in the regulation of genes encoding the NMDA-, AMPA-, and KA- receptor subunits and the inhibitory GABA(A) receptor. Deletion of gene for either Satb1 or Satb2 homologous factors induces the expression of genes encoding the NMDA receptor subunits, thereby leading to higher amplitudes of Ca<sup>2+</sup>-signals in neurons derived from the Satb1-deficient (Satb1<sup>fl/+</sup> * Nex<sup>Cre/+</sup>) and Satb1-null mice (Satb1<sup>fl/fl</sup> * Nex<sup>Cre/+</sup>) in response to the selective agonist reducing the EC50 for the NMDA receptor. Simultaneously, there is an increase in the expression of the <i>Gria2</i> gene, encoding the AMPA receptor subunit, thus decreasing the Ca<sup>2+</sup>-signals of neurons in response to the treatment with a selective agonist (5-Fluorowillardiine (FW)). The Satb1 deletion increases the sensitivity of the KA receptor to the agonist (domoic acid), in the cortical neurons of the Satb1-deficient mice but decreases it in the Satb1-null mice. At the same time, the Satb2 deletion decreases Ca<sup>2+</sup>-signals and the sensitivity of the KA receptor to the agonist in neurons from the Satb1-null and the Satb1-deficient mice. The Satb1 deletion affects the development of the inhibitory system of neurotransmission resulting in the suppression of the neuron maturation process and switching the GABAergic responses from excitatory to inhibitory, while the Satb2 deletion has a similar effect only in the Satb1-null mice. We show that the Satb1 and Satb2 transcription factors are involved in the regulation of the transmission of excitatory signals and inhibition of the neuronal network in the cortical cell culture.https://www.mdpi.com/1422-0067/22/11/5968Satb1Satb2calciumglutamate receptorsGABA-receptorsgene deletion |
| spellingShingle | Egor A. Turovsky Maria V. Turovskaya Evgeniya I. Fedotova Alexey A. Babaev Victor S. Tarabykin Elena G. Varlamova Role of Satb1 and Satb2 Transcription Factors in the Glutamate Receptors Expression and Ca<sup>2+</sup> Signaling in the Cortical Neurons In Vitro International Journal of Molecular Sciences Satb1 Satb2 calcium glutamate receptors GABA-receptors gene deletion |
| title | Role of Satb1 and Satb2 Transcription Factors in the Glutamate Receptors Expression and Ca<sup>2+</sup> Signaling in the Cortical Neurons In Vitro |
| title_full | Role of Satb1 and Satb2 Transcription Factors in the Glutamate Receptors Expression and Ca<sup>2+</sup> Signaling in the Cortical Neurons In Vitro |
| title_fullStr | Role of Satb1 and Satb2 Transcription Factors in the Glutamate Receptors Expression and Ca<sup>2+</sup> Signaling in the Cortical Neurons In Vitro |
| title_full_unstemmed | Role of Satb1 and Satb2 Transcription Factors in the Glutamate Receptors Expression and Ca<sup>2+</sup> Signaling in the Cortical Neurons In Vitro |
| title_short | Role of Satb1 and Satb2 Transcription Factors in the Glutamate Receptors Expression and Ca<sup>2+</sup> Signaling in the Cortical Neurons In Vitro |
| title_sort | role of satb1 and satb2 transcription factors in the glutamate receptors expression and ca sup 2 sup signaling in the cortical neurons in vitro |
| topic | Satb1 Satb2 calcium glutamate receptors GABA-receptors gene deletion |
| url | https://www.mdpi.com/1422-0067/22/11/5968 |
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