GPR6 Membrane Protein Introduction

Introduction of GPR6

GPR6 is a protein encoded by the GPR6 gene which belongs to the G protein-coupled receptor family of transmembrane receptors. During the past years, GPR6 has been widely studied. It has been reported that GPR6 is both constitutively active but in addition is further activated by sphingosine-1-phosphate. And GPR6 could up-regulate cyclic AMP levels and promote neurite outgrowth.

Function of GPR6 Membrane Protein

GPR6 belongs to the family of constitutively active Gs-coupled G protein-coupled receptors (GPCRs) that also includes GPR3 and GPR12. Based on the anatomical location of their expression, these receptors are involved in a wide array of functions such as neurite growth, amyloid processing, appetitive learning behavior and meiotic arrest of oocytes. And the diverse functions of this family of receptors appear to be mediated by their constitutive activity and their ability to maintain elevated intracellular cyclic AMP concentration. In the past years, the functions and applications of GPR6 have been widely studied. It has been reported that GPR6 is highly enriched in the striatal region of the adult mammalian brain, suggesting that this receptor may play a role in locomotor and/or reward-related behaviors. GPR6 knock-out mice don’t show overt locomotor aberration but showed an increased propensity to acquire appetitive learning behavior. Furthermore, GPR6 may also be expressed in intracellular compartments as GFP-tagged GPR6 was found predominantly between plasma membrane markers and nuclei.

Fig.1 G-protein-coupled receptor and G-protein. (Sontag, E. D.)

Application of GPR6 Membrane Protein in Literature

1. Laun A.S., Song ZH. GPR3 and GPR6, novel molecular targets for cannabidiol. Biochemical and biophysical research communications. 2017, 490(1):17-21. PubMed ID: 28571738
   
   

   This article suggests that GPR6 is a novel molecular target for cannabidiol. It indicates that CBD could act as a novel inverse agonist on GPR6 and some of the potential therapeutic effects of CBD (e.g. treatment of Alzheimer's disease and Parkinson's disease) may be mediated through GPR6 receptors.

2. Benoit M.E., et.al. C1q-induced LRP1B and GPR6 proteins expressed early in Alzheimer disease mouse models, are essential for the C1q-mediated protection against amyloid-β neurotoxicity. Journal of Biological Chemistry. 2013, 288(1):654-65. PubMed ID: 23150673
   
   

   This article identifies pathways by which C1q, up-regulated in vivo early in response to injury without the coordinate induction of other complement components, can induce a program of gene expression that promotes neuroprotection and thus may provide protection against Aβ in preclinical stages of the AD and other neurodegenerative processes.

3. Prasad B.M., et.al. Methods to detect cell surface expression and constitutive activity of GPR6. InMethods in enzymology. 2010, 484: 179-195. Academic Press. PubMed ID: 21036233
   
   

   This report introduces a series of methods which can be used to detect cell surface expression and constitutive activity of GPR6.

4. Padmanabhan S., et.al. Constitutively active GPR6 is located in the intracellular compartments. FEBS letters. 2009, 583(1):107-12. PubMed ID: 19059244
   
   

   This article suggests that GPR6 is primarily located in intracellular compartments. What’s more, it indicates that GPR6 can signal from intracellular compartments.

5. Ignatov A., et.al. Sphingosine-1-phosphate is a high-affinity ligand for the G protein-coupled receptor GPR6 from mouse and induces intracellular Ca²⁺ release by activating the sphingosine-kinase pathway. Biochemical and biophysical research communications. 2003, 311(2):329-36. PubMed ID: 14592418
   
   

   This article identifies the mouse orthologue of human GPR6 as a new member of the lysophospholipid-receptor family. It suggests that sphingosine-1-phosphate (S1P) could activate GPR6 with high specificity and nanomolar affinity.

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Reference

1. Sontag, E. D. Molecular Systems Biology and Dynamics: An Introduction for non-Biologists.

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