G Protein-Coupled Receptor 37 Like 1 Protein

G Protein-Coupled Receptor 37 Like 1 Protein

Introduction

G Protein Coupled Receptor 37 Like 1 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-protein"> [@zhang2018]
<div class="infobox-header">G Protein-Coupled Receptor 37 Like 1 (GPR37L1)</div> [@sardi2011]
<div class="infobox-content"> [@zhang2020]
<table> [@zheng2019]
<tr><th>Protein Name</th><td>G Protein-Coupled Receptor 37 Like 1</td></tr> [@koh2022]
<tr><th>Gene</th><td>[GPR37L1](/genes/gpr37l1)</td></tr> [@lundius2014]
<tr><th>UniProt ID</th><td>[O14924](https://www.uniprot.org/uniprotkb/O14924/entry)</td></tr> [@pisani2021]
<tr><th>Molecular Weight</th><td>67 kDa</td></tr>
<tr><th>Subcellular Localization</th><td>Endoplasmic Reticulum, Cell Membrane</td></tr>
<tr><th>Protein Family</th><td>GPR37 family, Class A GPCR</td></tr>
<tr><th>Primary G Protein</th><td>Gαs</td></tr>
<tr><th>Tissue Expression</th><td>Brain (oligodendrocytes, neurons), peripheral nervous system</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>
</div>

Overview

G Protein-Coupled Receptor 37 Like 1 Protein

Introduction

G Protein Coupled Receptor 37 Like 1 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-protein"> [@zhang2018]
<div class="infobox-header">G Protein-Coupled Receptor 37 Like 1 (GPR37L1)</div> [@sardi2011]
<div class="infobox-content"> [@zhang2020]
<table> [@zheng2019]
<tr><th>Protein Name</th><td>G Protein-Coupled Receptor 37 Like 1</td></tr> [@koh2022]
<tr><th>Gene</th><td>[GPR37L1](/genes/gpr37l1)</td></tr> [@lundius2014]
<tr><th>UniProt ID</th><td>[O14924](https://www.uniprot.org/uniprotkb/O14924/entry)</td></tr> [@pisani2021]
<tr><th>Molecular Weight</th><td>67 kDa</td></tr>
<tr><th>Subcellular Localization</th><td>Endoplasmic Reticulum, Cell Membrane</td></tr>
<tr><th>Protein Family</th><td>GPR37 family, Class A GPCR</td></tr>
<tr><th>Primary G Protein</th><td>Gαs</td></tr>
<tr><th>Tissue Expression</th><td>Brain (oligodendrocytes, neurons), peripheral nervous system</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>
</div>

Overview

G Protein-Coupled Receptor 37 Like 1 (GPR37L1), also known as ETBR-like protein 1 (ETBL1), is a member of the GPR37 family of G protein-coupled receptors. GPR37L1 is predominantly expressed in oligodendrocytes and [astrocytes](/entities/astrocytes) in the central nervous system, where it plays important roles in myelination, oligodendrocyte differentiation, and neuroprotection. Notably, GPR37L1 has been implicated in the pathogenesis of Parkinson's disease (PD), multiple system atrophy (MSA), and other neurodegenerative disorders.

Structure

GPR37L1 is a Class A (rhodopsin-like) GPCR with the canonical seven transmembrane domain architecture:

The receptor contains several structural features unique to the GPR37 family, including an extended N-terminus (~200 amino acids) and a DRY motif in TM3 that regulates G protein coupling.

Molecular Function

G Protein Coupling

GPR37L1 signals primarily through Gαs proteins to activate adenylyl cyclase and increase intracellular cAMP levels. This signaling cascade can:

• Promote oligodendrocyte differentiation via PKA activation
• Modulate myelination through cAMP-dependent pathways
• Regulate neuronal survival through CREB activation

Protein Interactions

GPR37L1 interacts with several proteins relevant to neurodegeneration:

Post-translational Modifications

• N-linked glycosylation: Multiple sites in the N-terminal domain
• Ubiquitination: Targeted by parkin for proteasomal degradation
• Phosphorylation: C-terminal serine/threonine residues can be phosphorylated

Normal Function

Oligodendrocyte Biology

GPR37L1 is highly expressed in oligodendrocyte precursor cells (OPCs) and mature oligodendrocytes:

• Promotes oligodendrocyte differentiation: cAMP signaling promotes OPC differentiation into mature myelinating oligodendrocytes
• Regulates myelination: GPR37L1 knockout mice show hyp myelination and reduced myelin thickness
• Myelin maintenance: Continuous GPR37L1 signaling is required for myelin homeostasis

Neuronal Function

In neurons, GPR37L1:

• Modulates dopaminergic neuron survival
• Regulates synaptic plasticity through presynaptic mechanisms
• May function as a co-receptor for neurotrophic factors

Glial-Neuronal Communication

GPR37L1 participates in cross-talk between astrocytes/oligodendrocytes and neurons, supporting neuronal metabolic and trophic support.

Role in Disease

Parkinson's Disease

GPR37L1 accumulates in Lewy bodies in PD brains, and genetic studies have identified GPR37L1 variants associated with PD risk. GPR37L1 knockout mice display:

• Enhanced vulnerability to MPTP-induced dopaminergic neurodegeneration
• Behavioral deficits including reduced locomotion
• Altered striatal dopamine signaling

Multiple System Atrophy

GPR37L1 is a major component of glial cytoplasmic inclusions (GCIs) in MSA, the hallmark oligodendroglial inclusions. GPR37L1 aggregation:

• Reflects oligodendrocyte dysfunction in MSA
• May contribute to myelin degeneration
• Correlates with disease severity

Other Neurodegenerative Disorders

• Progressive supranuclear palsy (PSP): GPR37L1 inclusions in oligodendrocytes
• Amyotrophic lateral sclerosis (ALS): Altered expression in spinal cord
• Huntington's disease: Dysregulated in striatum

Therapeutic Implications

Drug Targets

Gene Therapy

AAV-mediated GPR37L1 delivery to enhance cAMP signaling in oligodendrocytes is being explored for MSA and PD.

Biomarker Potential

GPR37L1 levels in CSF may serve as a biomarker for oligodendrocyte dysfunction in MSA and PD.

Animal Models

GPR37L1 Knockout Mice

• Viable and fertile but show hyp myelination
• Reduced myelin thickness in corpus callosum
• Enhanced susceptibility to dopaminergic toxins
• Behavioral deficits in locomotor tests

Transgenic Models

• GPR37L1 overexpression leads to aggregation and toxicity
• Used to study GPR37L1 pathophysiology

Research Directions

• Development of selective GPR37L1 ligands
• Understanding GPR37L1 aggregation mechanisms
• GPR37L1-based biomarkers for oligodendrocyte disorders
• Gene therapy approaches for MSA and PD

Background

The study of G Protein Coupled Receptor 37 Like 1 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

See Also

• GPR37L1 Gene
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Multiple System Atrophy](/diseases/multiple-system-atrophy)
• Oligodendrocyte
• [Myelin](/mechanisms/myelin-integrity)
• G Protein-Coupled Receptor Signaling
• Parkin Gene

External Links

• [UniProt - GPR37L1](https://www.uniprot.org/uniprotkb/O14924/entry)
• [NCBI Protein - GPR37L1](https://www.ncbi.nlm.nih.gov/protein)
• [GeneCards - GPR37L1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=GPR37L1)
• [Human Protein Atlas - GPR37L1](https://www.proteinatlas.org/ENSG00000135597-GPR37L1)

References