NFAT4 is expressed in primary astrocytes and activated by glutamate.
Calcium signaling is a critical component of astrocyte activation but little information is available regarding the identity and function of transcriptional targets of calcium signaling in these cells. As a first step in elucidating the mechanisms that astrocytes use to regulate transcription in response to raised intracellular calcium concentrations, we have investigated expression and activation of the calcium activated transcription factors of the NFAT family. We report here that NFAT4 is expressed in U373 astrocytoma cells and in primary cultures of astrocytes. Treatment of U373 cells or primary astrocytes with the calcium ionophore A23187, or the neurotransmitter glutamate, leads to NFAT nuclear translocation and increased DNA binding to a NFAT consensus site through a cyclosporin A-sensitive process. These data suggest that NFAT4 functions as a calcium-responsive transcription factor in astrocytes.
Jones
Elizabeth A
EA
Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.
Sun
Doug
D
Kobierski
Linda
L
Symes
Aviva J
AJ
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D003593:Cytoplasm / Q000502:physiology; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D051381:Rats; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014178:Translocation, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D007476:Ionophores; D050778:NFATC Transcription Factors; C494008:NFATC3 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D000001:Calcimycin