Neural Expression of G Protein-coupled Receptors GPR3, GPR6, and GPR12 Up-regulates Cyclic AMP Levels and Promotes Neurite Outgrowth*

  title={Neural Expression of G Protein-coupled Receptors GPR3, GPR6, and GPR12 Up-regulates Cyclic AMP Levels and Promotes Neurite Outgrowth*},
  author={Shigeru Tanaka and Kenji Ishii and Kazue Kasai and Sung Ok Yoon and Yoshinaga Saeki},
  journal={Journal of Biological Chemistry},
  pages={10506 - 10515}
Cyclic AMP regulates multiple neuronal functions, including neurite outgrowth and axonal regeneration. GPR3, GPR6, and GPR12 make up a family of constitutively active G protein-coupled receptors (GPCRs) that share greater than 50% identity and 65% similarity at the amino acid level. They are highly expressed in the central nervous system, and their expression in various cell lines results in constitutive stimulation of cAMP production. When the constitutively active GPCRs were overexpressed in… 
The Subcellular Dynamics of the Gs-Linked Receptor GPR3 Contribute to the Local Activation of PKA in Cerebellar Granular Neurons
Results suggested that GPR3 was transported along the neurite and contributed to the local activation of PKA in CGN development, which may affect local neuronal functions, including neuronal differentiation and maturation.
Involvement of GPR12 in the regulation of cell proliferation and survival
Heterologous GPR 12 expression was demonstrated to promote proliferation and survival in human embryonic kidney 293 cells and it was found that GPR12 promoted cell survival under serum deprivation, indicating that G PR12 may play a role in cell proliferation and Survival.
Characterization of an Orphan G Protein-coupled Receptor, GPR20, That Constitutively Activates Gi Proteins*
It is demonstrated that GPR20 is constitutively active in the absence of ligand, leading to continuous activation of its coupled G proteins, including Gi/o proteins, without ligand stimulation.
Identification of a Novel Small-Molecule Agonist for Human G Protein–Coupled Receptor 3
Diphenyleneiodonium chloride (DPI) was identified as a novel and specific agonist of GPR3, which provides a useful tool for further study of this orphan GPCR.
Regulation of Constitutive GPR3 Signaling and Surface Localization by GRK2 and β-arrestin-2 Overexpression in HEK293 Cells
It is demonstrated that exogenously-expressed GPR3 localizes to the cell membrane and undergoes internalization in HEK293 cells and can be silenced by GRK2/β-arrestin overexpression, and strongly implicate the serine and/or threonine residues in the third intracellular loop in the regulation of G PR3 activity.
Sphingosine 1-phosphate acts as an activator for the porcine Gpr3 of constitutively active G protein-coupled receptors
Findings suggest the porcine Gpr3, Gpr6, and Gpr12 genes are identified as a subfamily of G protein-coupled receptors, and porcines GPR3 was a constitutively active Gprotein-Coupled receptor.


Role of the G-Protein-Coupled Receptor GPR12 as High-Affinity Receptor for Sphingosylphosphorylcholine and Its Expression and Function in Brain Development
It is hypothesize that sphingosylphosphorylcholine, most likely by interaction with GPR12, has positive effects on the differentiation and maturation of postmitotic neurons and that it may also influence the proliferation of neuronal precursor cells.
A protein kinase A–dependent molecular switch in synapsins regulates neurite outgrowth
It is shown that the nerve growth–promoting action of cAMP/PKA is mediated in part by the phosphorylation of synapsins at a single amino acid residue, providing a potential molecular approach for stimulating neuron regeneration, after injury and in neurodegenerative diseases.
Isolation and chromosomal localization of a novel human G-protein-coupled receptor (GPR3) expressed predominantly in the central nervous system.
Degenerate oligonucleotide primers designed against known G-protein-coupled receptors were used in polymerase chain reaction amplification to isolate a novel receptor sequence (R4) from a rat
Molecular cloning of an orphan G-protein-coupled receptor that constitutively activates adenylate cyclase.
The mouse ACCA (mACCA) was therefore recloned by PCR, and expression of mACCA in Cos-7 cells demonstrated that the mouse receptor behaved similarly as a constitutive activator of adenylate cyclase.
cAMP-Mediated Regulation of Neurotrophin-Induced Collapse of Nerve Growth Cones
The results suggest the presence of cross-talk between Ca2+- and cAMP-signaling pathways involved in the collapsing action of neurotrophins, in which the camp-pathway regulates the Ca2-mediated signal transduction required for BDNF-induced collapse.
Protein kinase A phosphorylation of RhoA mediates the morphological and functional effects of cyclic AMP in cytotoxic lymphocytes.
It is demonstrated here that cAMP‐dependent protein kinase A (PKA) phosphorylates RhoA in its C‐terminal region, on serine residue 188, and this phosphorylation supports the existence of an alternative pathway for terminating RHoA signalling whereby GTP‐bound Rho a, when phosphorylated, could be separated from its putative effector(s) independently of its GTP/GDP cycling.
A Highly Effective Dominant Negative αs Construct Containing Mutations That Affect Distinct Functions Inhibits Multiple Gs-coupled Receptor Signaling Pathways*
  • C. Berlot
  • Biology, Chemistry
    The Journal of Biological Chemistry
  • 2002
Results lead to two conclusions about receptor-G protein signaling: first, individual receptors have access to multiple types of G proteins in HEK-293 cell membranes and second, different G protein α subunits can compete with each other for binding to the same receptor.