Genetic and epigenetic control of the Na-G ion channel expression in glia.
The Na-G ion channel, previously cloned from a rat astroglia cDNA library, belongs to a new family of ion channels, related to but distinct from the predominant brain and muscle fast voltage-gated Na(+) channels. In vivo, the corresponding transcripts are widely expressed in peripheral nervous system neurons and glia, but only in selected subpopulations of neuronal and glia-like cells of the central nervous system. In the present report, we show that Na-G messenger RNA level in astrocyte and Schwann cell cultures is modulated in a cell-specific manner by several growth factors, hormones, and intracellular second messengers pathways. Striking changes in transcript level were observed in the two types of glia in response to protein-kinase A activation and to treatment with the neuregulin glial growth factor, indicating regulation of the Na-G gene by neuroglial signaling. By transient transfection of Na-G/reporter constructs into cultured cells, we show that a short genomic region, encompassing the first exon and 375 bp upstream, bears a high glial-specific transcriptional activity while part of the first intron behaves as a negative regulatory element. In vivo footprinting experiments revealed binding of glial-specific nuclear factors to several sites of the Na-G promoter region. Finally, Na-G/reporter constructs are shown to sustain a low but reproducible transcriptional response to cAMP, accounting in part for the elevation in mRNA level elicited by cAMP in Schwann cells and its reduction in astrocytes.
Gautron
S
S
Biochimie Cellulaire, CNRS FRE 2242, Collège de France, 11 Place M. Berthelot, 75005 Paris, France. gautron@im3.inserm.fr
Gruszczynski
C
C
Koulakoff
A
A
Poiraud
E
E
Lopez
S
S
Cambier
H
H
Dos Santos
G
G
Berwald-Netter
Y
Y
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology*; D001483:Base Sequence; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D018983:DNA Footprinting; D003850:Deoxyribonuclease I; D003907:Dexamethasone / Q000494:pharmacology; D005091:Exons; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology; D007438:Introns; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D012583:Schwann Cells / Q000166:cytology / Q000502:physiology*; D015222:Sodium Channels / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D014162:Transfection; D061566:Voltage-Gated Sodium Channels
D005938:Glucocorticoids; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C402116:Scn7a protein, rat; D015222:Sodium Channels; D061566:Voltage-Gated Sodium Channels; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003907:Dexamethasone; D017868:Cyclic AMP-Dependent Protein Kinases; D003850:Deoxyribonuclease I