Faculty Collaboration Database

Specificity protein 4 (Sp4) regulates the transcription of AMPA receptor subunit GluA2 (Gria2). Biochim Biophys Acta 2014 Jun;1843(6):1196-206

Date

03/01/2014

Pubmed ID

24576410

Pubmed Central ID

PMC4024218

DOI

10.1016/j.bbamcr.2014.02.008

Scopus ID

2-s2.0-84896463345 (requires institutional sign-in at Scopus site)   18 Citations

Abstract

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.

Author List

Priya A, Johar K, Nair B, Wong-Riley MT

MESH terms used to index this publication - Major topics in bold

Animals
Base Sequence
Binding Sites
Blotting, Western
Chromatin Immunoprecipitation
Electrophoretic Mobility Shift Assay
Gene Expression Regulation, Neoplastic
Luciferases
Mice
Molecular Sequence Data
Neuroblastoma
Promoter Regions, Genetic
Protein Subunits
RNA, Messenger
Real-Time Polymerase Chain Reaction
Receptors, AMPA
Reverse Transcriptase Polymerase Chain Reaction
Sp1 Transcription Factor
Sp3 Transcription Factor
Sp4 Transcription Factor
Transcription, Genetic
Tumor Cells, Cultured