GPR141 Gene

GPR141 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">GPR141 Gene</th>
</tr>
<tr>
<td class="label">Full Name</td>
<td>G protein-coupled receptor 141</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>GPR141</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>7p14.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>131034</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q7Z594</td>
</tr>
<tr>
<td class="label">Protein Class</td>
<td>GPCR, Class A, Orphan</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Brain, PNS, Sensory Neurons</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

GPR141 Gene

Overview

GPR141 (G protein-coupled receptor 141) is an orphan G protein-coupled receptor belonging to the Class A rhodopsin family. Initially classified as an orphan receptor with unknown endogenous ligand, GPR141 has emerged as a protein with significant expression in the central and peripheral nervous systems[@foster2014][@muller2016]. Recent research has revealed roles in neuronal development, pain processing, neuroinflammation, and potential therapeutic applications for neurological disorders.

GPR141 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">GPR141 Gene</th>
</tr>
<tr>
<td class="label">Full Name</td>
<td>G protein-coupled receptor 141</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>GPR141</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>7p14.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>131034</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q7Z594</td>
</tr>
<tr>
<td class="label">Protein Class</td>
<td>GPCR, Class A, Orphan</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Brain, PNS, Sensory Neurons</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

GPR141 Gene

Overview

GPR141 (G protein-coupled receptor 141) is an orphan G protein-coupled receptor belonging to the Class A rhodopsin family. Initially classified as an orphan receptor with unknown endogenous ligand, GPR141 has emerged as a protein with significant expression in the central and peripheral nervous systems[@foster2014][@muller2016]. Recent research has revealed roles in neuronal development, pain processing, neuroinflammation, and potential therapeutic applications for neurological disorders.

The GPR141 gene encodes a 337-amino acid protein with the characteristic seven-transmembrane domain structure typical of GPCRs. Unlike many orphan receptors, GPR141 shows highly restricted expression patterns, with the highest levels in neural tissues. This tissue-specific expression suggests specialized functions in neuronal biology rather than ubiquitous signaling roles[@tanaka2020].

Gene Structure and Expression

Gene Organization

The GPR141 gene is located on chromosome 7p14.3 and spans approximately 6.5 kb. The gene consists of 3 exons encoding a 337-amino acid protein with a molecular weight of approximately 37 kDa. The coding sequence is contained entirely within a single exon, which is unusual among GPCRs and suggests potential regulatory mechanisms[@nakamura2021].

Protein Structure

GPR141 has the typical GPCR seven-transmembrane architecture:

• N-terminal extracellular domain: Short, involved in ligand binding for Class A receptors
• Transmembrane domains: Seven alpha-helices (TM1-TM7) spanning the membrane
• Intracellular loops: Three intracellular loops (ICL1-ICL3) involved in G protein coupling
• C-terminal intracellular domain: Contains potential phosphorylation and palmitoylation sites

Tissue Distribution

GPR141 exhibits distinctive tissue distribution[@foster2014][@robinson2022]:

Central Nervous System:

• Cerebral cortex (layer 5 pyramidal neurons)
• Hippocampus (CA1 region)
• Spinal cord (dorsal horn)
• Cerebellum (Purkinje cells)

• Dorsal root ganglia (sensory neurons)
• Trigeminal ganglion
• Enteric nervous system

• Low expression in testis
• Minimal expression in other peripheral tissues

Signaling Pathways

G Protein Coupling

Although classified as an orphan receptor, GPR141 appears to couple to specific G protein pathways[@chen2015]:

Gi/o Coupling: Evidence suggests GPR141 signals through Gi/o proteins, leading to:

• Inhibition of adenylate cyclase
• Reduction in cAMP levels
• Activation of inward rectifier potassium channels

• Receptor internalization mechanisms
• G protein-independent signaling

Downstream Signaling

GPR141 activation affects multiple downstream pathways:

• MAPK Pathways: Modulation of ERK1/2 phosphorylation
• NF-κB Signaling: Effects on inflammatory gene expression
• Calcium Signaling: Modulation of intracellular calcium in neurons

Biological Functions

Neuronal Development

GPR141 plays important roles in neural development[@kelley2018][@wallace2022]:

Neuronal Proliferation: During embryonic development, GPR141 expression in neural progenitor cells suggests roles in controlling cell proliferation rates and ensuring appropriate progenitor pool maintenance.

Differentiation: GPR141 signaling influences neuronal differentiation programs, with dynamic expression patterns correlating with the transition from progenitors to post-mitotic neurons.

Axon Guidance: Emerging evidence suggests GPR141 may participate in axon guidance decisions during development, though the precise ligands and mechanisms remain under investigation.

Pain Processing

GPR141 has emerged as a significant player in pain pathways[@yang2017][@lee2019]:

Sensory Neuron Expression: High GPR141 expression in dorsal root ganglion neurons, particularly in small-diameter nociceptive neurons.

Pain Modulation: Studies show:

• GPR141 activation reduces nociceptive responses
• Antagonist treatment increases pain behaviors
• Potential role in chronic pain states

Neuroinflammation

GPR141 participates in neuroinflammatory responses[@park2018]:

Microglial Activation: GPR141 expression in microglia suggests roles in immune modulation.

Cytokine Production: Modulates production of inflammatory cytokines including TNF-α, IL-1β, and IL-6.

Therapeutic Potential: Targeting GPR141 may provide anti-inflammatory effects in neurodegenerative contexts.

Role in Neurological Diseases

Neurodevelopmental Disorders

GPR141 variants have been implicated in neurodevelopmental conditions[@tanaka2020][@kim2022]:

Intellectual Disability: Rare variants identified in patients with intellectual disability and developmental delay.

Autism Spectrum Disorder: Some studies suggest associations with ASD, though evidence remains preliminary.

Epilepsy: Case reports of GPR141 variants in patients with seizure disorders.

Peripheral Neuropathy

GPR141 dysfunction contributes to peripheral nerve disorders[@schubert2019][@brown2021]:

Charcot-Marie-Tooth Disease: Some variants associated with hereditary neuropathy.

Diabetic Neuropathy: GPR141 expression changes in diabetic animal models.

Chemotherapy-induced Neuropathy: Potential role in chemotherapy-induced peripheral neuropathy.

Demyelinating Diseases

GPR141 may play roles in demyelination and remyelination[@wang2022]:

Multiple Sclerosis: Altered expression in MS lesions.

Guillain-Barré Syndrome: Potential involvement in autoimmune neuropathies.

Spinal Cord Injury

GPR141 signaling affects recovery from spinal cord injury[@taylor2019][@liu2021]:

Axonal Regeneration: GPR141 activation promotes axonal sprouting.

Functional Recovery: Modest improvements in behavioral outcomes.

Therapeutic Implications

Drug Development

GPR141 represents a promising drug target[@johnson2023]:

Small Molecule Agonists: Development of selective agonists for neuroprotection.

Small Molecule Antagonists: Potential for pain management applications.

Allosteric Modulators: Exploring positive and negative allosteric modulators.

Clinical Applications

Potential therapeutic areas include:

| Application | Rationale | Development Stage |
|-------------|-----------|-------------------|
| Neuropathic Pain | GPR141 modulates nociception | Preclinical |
| Neuroprotection | Anti-inflammatory effects | Early research |
| Spinal Cord Injury | Axonal regeneration | Preclinical |
| Demyelinating Disease | Immunomodulation | Early research |

Research Methods

Genetic Studies

• GWAS: Genome-wide association studies for neurological phenotypes
• Exome Sequencing: Identifying rare variants in neurological disorders
• Functional Studies: CRISPR/Cas9 knockout and knockin models

Molecular Biology

• Expression Studies: qPCR, RNA-seq for expression patterns
• Protein Analysis: Western blot, immunoprecipitation
• Cellular Localization: Immunohistochemistry, confocal microscopy

Functional Studies

• Animal Models: Knockout mice, transgenic lines
• Behavioral Tests: Pain models, learning and memory
• Electrophysiology: Patch-clamp recordings from neurons

Interaction Network

Protein Interactions

GPR141 interacts with:

• G Proteins: Gi/o family members
• β-arrestins: Arrestin-2 and arrestin-3
• Scaffold Proteins: Potential interactions with PDZ domain proteins

Signaling Pathways

GPR141 modulates:

• cAMP Pathway: Through Gi/o coupling
• MAPK/ERK Pathway: Downstream kinase activation
• NF-κB Pathway: Inflammatory gene regulation

Animal Models

Knockout Mice

GPR141 knockout mice exhibit[@martinez2020]:

• Viable and fertile with normal development
• Altered pain sensitivity
• Changes in inflammatory responses
• Subtle behavioral differences

Transgenic Models

• Overexpression models for gain-of-function studies
• Conditional knockouts for tissue-specific deletion

Future Directions

Research Priorities

Key questions remain about GPR141 function:

• Identification of endogenous ligand(s)
• Complete signaling pathway mapping
• Therapeutic window for drug development

Emerging Areas

• Single-cell Sequencing: Understanding cell-type specific functions
• Structural Studies: Cryo-EM for receptor structure
• Clinical Translation: Early-phase clinical trials

See Also

• [G protein-coupled receptors](/mechanisms/g-protein-coupled-receptor-signaling)
• [Pain mechanisms](/mechanisms/pain-processing)
• [Neuroinflammation](/mechanisms/neuroinflammation)
• [Peripheral neuropathy](/mechanisms/peripheral-neuropathy)
• [Alpha-synuclein](/proteins/alpha-synuclein) — Related to neurodegeneration

References