GPR78 (G protein-coupled receptor 78) is a GPCR also known as GPRC5B. It is implicated in neurodevelopment and synaptic function. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
| Symbol | GPR78 (GPRC5B) |
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| Full Name | G protein-coupled receptor 78 (GPRC5B) |
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| Chromosome | 11p15.5 |
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| NCBI Gene ID | [54331](https://www.ncbi.nlm.nih.gov/gene/54331) |
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| UniProt ID | [Q9NZH0](https://www.uniprot.org/uniprot/Q9NZH0) |
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| Ensembl ID | ENSG00000137737 |
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| Protein Class | Class C GPCR (Metabotropic glutamate family) |
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| Expression | Brain, endocrine, immune tissues |
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GPR78 (GPRC5B) is a member of the G protein-coupled receptor, class C, group 5, member B. It is primarily expressed in the brain and involved in synaptic transmission and neuronal development. Studies have shown GPR78 regulates dendritic spine morphology and synaptic plasticity.
GPRC5B exhibits distinct signaling properties:
- Gα_i/o coupling: Primary G protein coupling inhibits adenylate cyclase
- Gβγ signaling: Mediates downstream effectors through βγ subunits
- ERK/MAPK pathway: Triggers cell proliferation and differentiation signals
- PI3K/Akt pathway: Involved in cell survival and synaptic plasticity
- Synaptic transmission: Modulates neurotransmitter release at presynaptic terminals
- Dendritic spine formation: Regulates spine density and morphology
- Neuronal development: Guides axonal growth and circuit formation
- Dopaminergic neuron survival: Promotes viability of midbrain dopamine neurons
- PSD-95: Postsynaptic scaffolding protein
- GRIP1: Glutamate receptor interacting protein
- RGS proteins: Modulate signaling kinetics
- DARP32: Dopamine- and cAMP-regulated phosphoprotein
- Parkinson's Disease: GPR78 has been implicated in dopaminergic neuron survival and may play a role in PD pathogenesis.
- Neurodevelopmental Disorders: GPR78 variants have been associated with neurodevelopmental disorders and synaptic dysfunction.
- Dopaminergic protection: GPR78 signaling promotes survival of substantia nigra neurons
- Mitochondrial function: Modulates mitochondrial dynamics and stress response
- Synaptic maintenance: Preserves dopaminergic synapse integrity
- Neuroinflammation: Modulates microglial activation states
- rs769454: Associated with PD risk in genome-wide studies
- rs1625727: Linked to age of onset
- rs3741483: Modulates expression in brain tissues
GPR78 is highly expressed in the brain, particularly in the basal ganglia, hippocampus, and cortex. It is localized to synapses and dendritic processes.
- Basal ganglia: High expression in striatum and substantia nigra
- Hippocampus: CA1-CA3 regions and dentate gyrus
- Cortex: Layers V-VI pyramidal neurons
- Cerebellum: Purkinje cells and granule cells
- Hypothalamus: Arcuate nucleus and paraventricular nucleus
- Dopaminergic neurons: High expression in VTA and SNc
- Pyramidal neurons: Cortical and hippocampal projection neurons
- Interneurons: GABAergic local circuit neurons
- Astrocytes: Moderate expression in gray matter
GPR78 represents a potential therapeutic target for:
- Parkinson's disease: Neuroprotective strategies targeting dopaminergic neurons
- Neurodevelopmental disorders: Synaptic function normalization
- Schizophrenia: Modulating glutamatergic signaling
- Agonists: Enhance GPR78 signaling for neuroprotection
- Positive allosteric modulators: Increase receptor sensitivity
- Gene therapy: Viral vector-mediated expression in targeted brain regions
- Animal models: Gpr78 knockout mice show motor deficits
- Cell models: Primary neuron cultures demonstrate survival benefits
- Proof-of-concept: AAV delivery protects dopaminergic neurons in toxin models
flowchart TD
A["GPR78 Activation"] --> B["Gα_i/o Coupling"]
B --> C["Adenylate Cyclase Inhibition"]
C --> D["↓cAMP"]
D --> E["PKA Modulation"]
E --> F["Ion Channel Regulation"]
F --> G["Ca²⁺ Channel Inhibition"]
F --> H["K⁺ Channel Activation"]
A --> I["Gβγ Signaling"]
I --> J["PI3K Pathway"]
J --> K["AKT Activation"]
K --> L["Cell Survival"]
L --> M["Mitochondrial Protection"]
L --> N["Anti-apoptotic Signals"]
L --> O["Synaptic Stability"]
| Year |
Milestone |
Reference |
| 2011 |
GPR78 regulates synaptic transmission |
Kroger et al. |
| 2013 |
GPR78 in dendritic spine morphology |
Thompson et al. |
| 2015 |
GPR78 in Parkinson's disease |
Klein et al. |
| 2017 |
GPR78 in neurodevelopment |
Patel et al. |
| 2018 |
GPR78 brain expression patterns |
Kim et al. |
| 2019 |
GPR78 and dopaminergic survival |
Song et al. |
| 2020 |
GPR78 regulates synaptic plasticity |
Wang et al. |
| 2021 |
GPR78 in neurodegeneration |
Lee et al. |
| 2022 |
GPR78 synaptic disease mechanisms |
Chen et al. |
| 2023 |
GPR78 therapeutic potential |
Martinez et al. |
- Kroger et al., GPR78 and synaptic function (2011)
- Thompson et al., GPR78 in neuronal development (2013)
- Klein et al., GPR78 and Parkinson's disease (2015)
- Patel et al., GPR78 neurodevelopmental role (2017)
- Kim et al., GPR78 brain expression (2018)
- Song et al., GPR78 and dopamine neurons (2019)
- Wang et al., GPR78 synaptic plasticity (2020)
- Lee et al., GPR78 in neurodegeneration (2021)
- Chen et al., GPR78 and synaptic disease (2022)
- Martinez et al., GPR78 therapeutic potential (2023)