Faculty Collaboration Database

Specificity protein 4 functionally regulates the transcription of NMDA receptor subunits GluN1, GluN2A, and GluN2B. Biochim Biophys Acta 2013 Dec;1833(12):2745-2756

Date

07/23/2013

Pubmed ID

23871830

Pubmed Central ID

PMC3834217

DOI

10.1016/j.bbamcr.2013.07.002

Scopus ID

2-s2.0-84882799217 (requires institutional sign-in at Scopus site)   30 Citations

Abstract

N-Methyl-d-aspartate (NMDA) receptors are major glutamatergic receptors involved in most excitatory neurotransmission in the brain. The transcriptional regulation of NMDA receptors is not fully understood. Previously, we found that the GluN1 and GluN2B subunits of the NMDA receptor are regulated by nuclear respiratory factors 1 and 2 (NRF-1 and NRF-2). NRF-1 and NRF-2 also regulate all 13 subunits of cytochrome c oxidase (COX), a critical energy-generating enzyme, thereby coupling neuronal activity and energy metabolism at the transcriptional level. Specificity protein (Sp) is a family of transcription factors that bind to GC-rich regions, with Sp1, Sp3, and Sp4 all binding to the same cis- motifs. Sp1 and Sp3 are ubiquitously expressed, whereas Sp4 expression is restricted to neurons and testicular cells. Recently, we found that the Sp1 factor regulates all subunits of COX. The goal of the present study was to test our hypothesis that the Sp factors also regulate specific subunits of NMDA receptors, and that they function with NRF-1 and NRF-2 via one of three mechanisms: complementary, concurrent and parallel, or a combination of complementary and concurrent/parallel. By means of multiple approaches we found that Sp4 functionally regulated GluN1, GluN2A, and GluN2B, but not GluN2C. On the other hand, Sp1 and Sp3 did not regulate these subunits as previously thought. Our data suggest that Sp4 operates in a complementary and concurrent/parallel manner with NRF-1 and NRF-2 to mediate the tight coupling between energy metabolism and neuronal activity at the molecular level.

Author List

Priya A, Johar K, Wong-Riley MTT

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

Animals
Binding Sites
Carrier Proteins
Cell Nucleus
Cells, Cultured
Chromatin Immunoprecipitation
Computer Simulation
Gene Silencing
HeLa Cells
Humans
Membrane Potentials
Mice
Mutant Proteins
Mutation
Nerve Tissue Proteins
Neurons
Potassium Chloride
Promoter Regions, Genetic
Protein Binding
Receptors, N-Methyl-D-Aspartate
Sp1 Transcription Factor
Sp3 Transcription Factor
Sp4 Transcription Factor
Tetrodotoxin
Transcription, Genetic
Visual Cortex