Specificity protein 4 (Sp4) regulates the transcription of AMPA receptor subunit GluA2 (Gria2).
The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are important glutamatergic receptors mediating fast excitatory synaptic transmission in the brain. The regulation of the four subunits of AMPA receptors, GluA1-4, is poorly understood. Excitatory synaptic transmission is highly energy-demanding, and this energy is derived mainly from the oxidative pathway. Recently, we found that specificity factor regulates all subunits of cytochrome c oxidase (COX), a critical energy-generating enzyme. COX is also regulated by nuclear respiratory factor 1 (NRF-1), which transcriptionally controls the Gria2 (GluA2) gene of AMPA receptors. The goal of the present study was to test our hypothesis that Sp-factors (Sp1, Sp3, and/or Sp4) also regulate AMPA subunit genes. If so, we wish to determine if Sp-factors and NRF-1 function via a complementary, concurrent and parallel, or a combination of complementary and concurrent/parallel mechanism. By means of multiple approaches, including electrophoretic mobility shift and supershift assays, chromatin immunoprecipitation, promoter mutations, real-time quantitative PCR, and western blot analysis, we found that Sp4, but not Sp1 or Sp3, regulates the Gria2, but not Gria1, 3, or 4, subunit gene of the AMPA receptor in a concurrent and parallel manner with NRF-1. Thus, Sp4 and NRF-1 both mediate the tight coupling between neuronal activity and energy metabolism at the transcriptional level.
['Priya|Anusha|A|', 'Johar|Kaid|K|', 'Nair|Bindu|B|', 'Wong-Riley|Margaret T T|MT|']
D000818:Animals D001483:Base Sequence D001665:Binding Sites D015153:Blotting, Western D047369:Chromatin Immunoprecipitation D024202:Electrophoretic Mobility Shift Assay D015972:Gene Expression Regulation, Neoplastic D008156:Luciferases D051379:Mice D008969:Molecular Sequence Data D009447:Neuroblastoma D011401:Promoter Regions, Genetic D021122:Protein Subunits D012333:RNA, Messenger D060888:Real-Time Polymerase Chain Reaction D018091:Receptors, AMPA D020133:Reverse Transcriptase Polymerase Chain Reaction D016329:Sp1 Transcription Factor D051705:Sp3 Transcription Factor D051706:Sp4 Transcription Factor D014158:Transcription, Genetic D014407:Tumor Cells, Cultured
Specificity protein 4 Sp4 AMPA receptor GluA2 Gene regulation Transcription factor