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Updated: Mar 3, 2026

Subtype-selective Electroporation of Cortical Interneurons
Published on: August 18, 2014
GPR3 is an immediate-early gene-like GPCR regulating CREB-dependent neuronal differentiation
Shigeru Tanaka1, Fumiaki Ikawa1, Hiroko Shiraki1
1Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Abstract:
GPR3 is a constitutively active Gs-coupled receptor whose transcriptional regulation during neuronal differentiation has remained unclear. Here, we identify Gpr3 as an immediate-early gene-like transcript rapidly induced by nerve growth factor (NGF) and cAMP signaling in PC12 cells, exhibiting biphasic activation captured by native elongating transcript-cap analysis of gene expression (NET-CAGE) at a core promoter ∼200 bp upstream of the transcription start site (TSS). Five cAMP response elements (CREs) within the 1-kb regulatory region cooperatively mediated stimulus-responsive transcription, with p-CREB enrichment selectively occurring at the proximal -34 CRE. Early Gpr3 induction enhanced delayed Nr4a1-3 expression and promoted Synapsin1 (Syn1) transcription through an Nr4a1-dependent mechanism. In primary cortical neurons, Gpr3 deletion diminished the developmental upregulation of Nr4a1-3 and Syn1 and reduced SYN1-positive vesicle density. These findings indicate GPR3 as an activity-dependent cAMP amplifier that couples early CREB activation to transcriptional programs governing NR4A signaling and presynaptic maturation during neuronal differentiation.
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