Related Experiment Video
Updated: Mar 3, 2026
06:42
Subtype-selective Electroporation of Cortical Interneurons
Published on: August 18, 2014
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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.
Iscience
|March 2, 2026
Summary
G protein-coupled receptor 3 (GPR3) acts as an immediate-early gene during neuronal differentiation, rapidly responding to nerve growth factor (NGF) and cAMP. Its induction influences NR4A signaling and synaptic vesicle development.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- The transcriptional regulation of G protein-coupled receptor 3 (GPR3), a constitutively active Gs-coupled receptor, during neuronal differentiation is not well understood.
- Understanding GPR3's role is crucial for deciphering neuronal development pathways.
Purpose of the Study:
- To investigate the transcriptional regulation of GPR3 during neuronal differentiation.
- To elucidate the role of GPR3 in downstream signaling pathways and synaptic development.
Main Methods:
- Utilized PC12 cells and primary cortical neurons.
- Employed native elongating transcript-cap analysis of gene expression (NET-CAGE) to map transcription.
- Investigated cAMP response elements (CREs) and transcription factor binding (p-CREB).
- Performed gene deletion studies in primary neurons.
Main Results:
- Identified GPR3 as an immediate-early gene transcript rapidly induced by NGF and cAMP.
- Demonstrated cooperative mediation of transcription by five CREs, with p-CREB enrichment at the proximal -34 CRE.
- Showed that early GPR3 induction enhances NR4A1-3 expression and promotes Synapsin1 (Syn1) transcription via an NR4A1-dependent mechanism.
- Observed diminished NR4A1-3 and Syn1 upregulation and reduced SYN1-positive vesicle density in GPR3-deleted primary neurons.
Conclusions:
- GPR3 functions as an activity-dependent cAMP amplifier.
- GPR3 couples early CREB activation to transcriptional programs involving NR4A signaling.
- GPR3 plays a significant role in presynaptic maturation during neuronal differentiation.
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