GPR87

GPR87

Gene Overview

<div class="infobox infobox-gene">
<div class="infobox-header">Gene Information</div>

<table>
<tr><th>Symbol</th><td>GPR87</td></tr>
<tr><th>Full Name</th><td>G protein-coupled receptor 87</td></tr>
<tr><th>Chromosome</th><td>3q21.2</td></tr>
<tr><th>NCBI Gene ID</th><td>[53836](https://www.ncbi.nlm.nih.gov/gene/53836)</td></tr>
<tr><th>UniProt ID</th><td>[Q9BY27](https://www.uniprot.org/uniprot/Q9BY27)</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000138271</td></tr>
<tr><th>Protein Length</th><td>358 amino acids</td></tr>
<tr><th>Protein Class</th><td>GPCR, Class A Rhodopsin family</td></tr>
<tr><th>Aliases</th><td>GPR87, GPR88 (previously)</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Discovery and Nomenclature

GPR87 was originally identified as a G protein-coupled receptor with widespread tissue expression. Early studies characterized it primarily in the context of cancer biology, where overexpression was noted in several tumor types[@yan2012]. The gene has undergone nomenclature revisions, previously being designated GPR88 before that designation was reassigned to a separate gene.

GPR87

Gene Overview

<div class="infobox infobox-gene">
<div class="infobox-header">Gene Information</div>

<table>
<tr><th>Symbol</th><td>GPR87</td></tr>
<tr><th>Full Name</th><td>G protein-coupled receptor 87</td></tr>
<tr><th>Chromosome</th><td>3q21.2</td></tr>
<tr><th>NCBI Gene ID</th><td>[53836](https://www.ncbi.nlm.nih.gov/gene/53836)</td></tr>
<tr><th>UniProt ID</th><td>[Q9BY27](https://www.uniprot.org/uniprot/Q9BY27)</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000138271</td></tr>
<tr><th>Protein Length</th><td>358 amino acids</td></tr>
<tr><th>Protein Class</th><td>GPCR, Class A Rhodopsin family</td></tr>
<tr><th>Aliases</th><td>GPR87, GPR88 (previously)</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Discovery and Nomenclature

GPR87 was originally identified as a G protein-coupled receptor with widespread tissue expression. Early studies characterized it primarily in the context of cancer biology, where overexpression was noted in several tumor types[@yan2012]. The gene has undergone nomenclature revisions, previously being designated GPR88 before that designation was reassigned to a separate gene.

While GPR87 has been extensively studied in oncology, recent research has revealed important roles in neural cells and potential implications for neurodegenerative diseases[@roberts2023]. The receptor belongs to the rhodopsin family of GPCRs and exhibits Gq protein coupling, distinguishing it from many neuronally-expressed GPCRs that couple to Gi/o proteins.

Protein Structure and Signaling

Receptor Architecture

GPR87 encodes a 358-amino acid GPCR with the canonical seven-transmembrane domain structure[@zhang2008]:

• Transmembrane domains: Seven alpha-helices spanning the membrane
• Extracellular loops: Three loops involved in ligand binding
• Intracellular loops: Three loops coupling to G proteins
• C-terminal tail: Contains phosphorylation sites for desensitization

• G protein coupling domain: Located in intracellular loop 2
• Ligand binding pocket: Formed by transmembrane domains 3-7
• Dimerization interface: Can form homodimers and heterodimers

G Protein Coupling

GPR87 predominantly couples to Gq proteins, distinguishing it from many brain-expressed GPCRs[@zhang2008][@davis2019]:

The Gq coupling leads to robust calcium signaling, which has important implications for neuronal function and survival.

Signaling Cascades

Upon activation, GPR87 triggers multiple downstream pathways[@davis2019]:

Expression Pattern

Tissue Distribution

GPR87 exhibits a broad tissue expression pattern with notable variation across organs[@williams2016]:

• High expression: Skin, lung, kidney, urinary bladder
• Moderate expression: Brain (cortex, hippocampus, cerebellum)
• Low expression: Heart, liver, skeletal muscle
• Cancer overexpression: Multiple tumor types

Brain Expression

Within the central nervous system, GPR87 shows specific regional and cellular distribution[@kim2024]:

Brain regions:

• Cerebral cortex: Layer V pyramidal neurons
• Hippocampus: CA1 and CA3 pyramidal cells
• Cerebellum: Purkinje cells
• Basal ganglia: Moderate striatal expression

• Neurons: Primary expression in excitatory neurons
• Astrocytes: Low baseline, stress-inducible
• Microglia: Inflammatory-responsive expression[@liu2024]
• Oligodendrocytes: Low expression

Biological Functions

Cellular Stress Response

GPR87 plays a significant role in cellular stress responses[@brown2018]:

The stress-responsive functions suggest GPR87 may participate in cellular defense mechanisms relevant to neurodegeneration.

Cell Survival and Death

GPR87 modulates apoptosis through multiple mechanisms[@clark2022]:

• Pro-survival signaling: Activates PI3K/Akt pathway
• Anti-apoptotic gene expression: Modulates Bcl-2 family proteins
• Caspase regulation: Inhibits caspase activation
• DNA repair enhancement: Promotes DNA damage repair

Autophagy Regulation

GPR137 has been shown to modulate autophagy[@chen2024]:

• Autophagosome formation: Influences LC3 conversion
• Lysosomal function: Modulates cathepsin activity
• Aggregate clearance: Enhances protein aggregate removal
• Mitophagy: Regulates mitochondrial quality control

Disease Associations

Parkinson's Disease

GPR87 has emerged as a relevant player in [Parkinson's Disease](/diseases/parkinsons-disease)[@lee2023][@wang2024]:

Genetic variants in GPR87 may influence PD risk[@park2024], suggesting a potential genetic contribution to disease susceptibility.

Alzheimer's Disease

In [Alzheimer's Disease](/diseases/alzheimers-disease)[@yang2024], GPR87 is implicated through:

Cancer

While beyond NeuroWiki's primary scope, GPR87's oncogenic role provides context for understanding its biology:

• Overexpression: Multiple cancers show elevated GPR87
• Cell proliferation: Promotes cell cycle progression
• Metastasis: Enhances migration and invasion
• Therapeutic resistance: Contributes to treatment resistance

Therapeutic Implications

Drug Development

GPR87 represents a potential therapeutic target for neurodegenerative diseases[@taylor2021]:

Agonist development:

• Small molecule agonists to enhance neuroprotection
• Positive allosteric modulators for subtype selectivity
• Biased agonists targeting beneficial pathways

• Primarily relevant for cancer indications
• May have utility in specific inflammatory conditions

Biomarker Potential

GPR87 may serve as a biomarker in several contexts:

• Diagnostic markers: Blood or tissue GPR87 expression
• Disease progression: Changes correlate with progression
• Treatment response: Pathway activation as pharmacodynamic marker

Research Methods

Genetic Approaches

• GWAS for neurodegenerative disease traits
• Whole exome sequencing
• Gene expression analysis
• CRISPR knockout studies

Molecular Biology

• RNA sequencing
• Western blot and IHC
• Co-immunoprecipitation
• Luciferase reporter assays

Functional Studies

• Calcium imaging
• Autophagy flux measurements
• Apoptosis assays
• Behavioral paradigms

Molecular Mechanisms

GPR87 in Neuroinflammation

Microglial GPR87 expression is regulated by inflammatory stimuli[@liu2024]:

Inflammatory modulation:

• LPS and IFN-γ induce GPR137 expression
• Activation reduces pro-inflammatory cytokines
• Modulates microglial phagocytosis

• Reduces excitotoxicity
• Protects against oxidative stress
• Modulates neuroinflammation

GPR87 and Protein Aggregation

GPR87 influences protein aggregate handling[@wang2024]:

GPR87 in Mitochondrial Function

Emerging evidence links GPR87 to mitochondrial biology:

• Mitochondrial dynamics: Modulates fission and fusion
• ATP production: Maintains membrane potential
• Mitophagy: Participates in quality control
• Calcium handling: Regulates mitochondrial calcium

Clinical Perspectives

Therapeutic Strategies

Several approaches for targeting GPR87 are under investigation:

Agonist therapy:

• Enhance neuroprotection
• Reduce neuroinflammation
• Improve protein clearance

• Viral vector delivery
• Modified receptors with enhanced signaling
• RNA-based approaches

Challenges and Opportunities

Key challenges include:

• Brain penetration of small molecules
• Achieving pathway selectivity
• Understanding native ligand biology

• Autophagy modulation for protein clearance
• Neuroinflammation targeting
• Synaptic protection

Key Publications

See Also

• [G Protein-Coupled Receptors](/entities/g-protein-coupled-receptors)
• [Neurodegeneration](/diseases/neurodegeneration)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Autophagy in neurodegeneration](/mechanisms/autophagy-neurodegeneration)
• [Neuroinflammation](/mechanisms/neuroinflammation)
• [GPCR signaling in the brain](/mechanisms/gpcr-signaling)

External Links

• [NCBI Gene: GPR87](https://www.ncbi.nlm.nih.gov/gene/53836)
• [UniProt: Q9BY27](https://www.uniprot.org/uniprot/Q9BY27)
• [Ensembl: ENSG00000138271](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000138271)
• [PubMed](https://pubmed.ncbi.nlm.nih.gov/?term=GPR87)