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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 Goα, the α subunit of Go, on the expression of Cav2.2, 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 Cav2.2 gene. Overexpression of Goα inhibited neurite extension in F11 cells and simultaneously repressed the stimulatory effect of cAMP on the Cav2.2 gene expression to the basal level. Targeted mutation of the Goα gene also increased the level of Cav2.2 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. [Copyright &y& Elsevier]