Modulation of the N-type calcium channel gene expression by the alpha subunit of Go.
Go, a heterotrimeric G-protein, is enriched in brain and neuronal growth cones. Although several reports suggest that Go may be involved in modulation of neuronal differentiation, the precise role of Go is not clear. To investigate the function of Go in neuronal differentiation, we determined the effect of Goalpha, the alpha subunit of Go, on the expression of Ca(v)2.2, the pore-forming unit of N-type calcium channels, at the transcription level. Treatment with cyclic AMP (cAMP), which triggers neurite outgrowth in neuroblastoma F11 cells, increased the mRNA level and the promoter activity of the Ca(v)2.2 gene. Overexpression of Goalpha inhibited neurite extension in F11 cells and simultaneously repressed the stimulatory effect of cAMP on the Ca(v)2.2 gene expression to the basal level. Targeted mutation of the Goalpha gene also increased the level of Ca(v)2.2 in the brain. These results suggest that Go may regulate neuronal differentiation through modulation of gene expression of target genes such as N-type calcium channels.
Kim
Bum-Jun
BJ
Department of Anatomy, School of Medicine, Ajou University, San 5, Wonchon-dong, Paldal-gu, Suwon, 442-749, South Korea.
Ghil
Sung-Ho
SH
Kim
Min-Ji
MJ
Yun Park
So
S
Kim
Dong-Sun
DS
Hwan Kim
Sung
S
Chin
Hemin
H
Birnbaumer
Lutz
L
Jiang
Meisheng
M
Hong
Sung Youl
SY
Suh-Kim
Haeyoung
H
Lee
Young-Don
YD
D000818:Animals; D001921:Brain / Q000196:embryology* / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D018390:Gene Targeting; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D020864:Calcium Channels, N-Type; D021122:Protein Subunits; D012333:RNA, Messenger; D000242:Cyclic AMP; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D020962:Heterotrimeric GTP-Binding Proteins