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.
Biochimie Cellulaire, CNRS FRE 2242, Collège de France, 11 Place M. Berthelot, 75005 Paris, France. gautron@im3.inserm.fr
S
S
Gautron
C
C
Gruszczynski
A
A
Koulakoff
E
E
Poiraud
S
S
Lopez
H
H
Cambier
G
G
Dos Santos
Y
Y
Berwald-Netter
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