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Desensitized D2 autoreceptors are resistant to trafficking
Brooks G Robinson1, James R Bunzow1, Jonathan B Grimm2
1The Vollum Institute, Oregon Health and Science University, 3181S.W. Sam Jackson Pk. Rd., Portland, OR, 97239, USA.
Scientific Reports
|July 1, 2017
Summary
Dopamine D2 autoreceptors on dopamine neurons cluster unevenly and do not internalize upon desensitization, unlike in other neurons. This suggests a unique, regulated localization of these inhibitory G protein-coupled receptors in the brain.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Dopamine D2 autoreceptors (a type of inhibitory G protein-coupled receptor) regulate dopamine neuron excitability.
- Understanding their precise localization and trafficking is crucial for comprehending dopaminergic system function.
Purpose of the Study:
- To investigate the localization and distribution of dopamine D2 autoreceptors in living midbrain dopamine neurons.
- To examine the physiological signaling, desensitization, and internalization patterns of tagged D2 receptors.
Main Methods:
- Utilized GFP-tagged D2 receptors to visualize and track receptor behavior in real-time within dopamine neurons.
- Compared receptor internalization in dopamine neurons versus locus coeruleus neurons and with µ-opioid receptors in dopamine neurons.
Main Results:
- GFP-tagged D2 receptors exhibited uneven clustering on the soma and dendrites of dopamine neurons in the substantia nigra pars compacta (SNc).
- Tagged D2 receptors showed normal physiological signaling and desensitization compared to wild-type receptors.
- Unexpectedly, desensitized D2 receptors on dopamine neurons were not internalized, contrasting with their internalization in locus coeruleus neurons and µ-opioid receptors in dopamine neurons.
Conclusions:
- The unique distribution and lack of agonist-induced internalization of D2 receptors on dopamine neurons suggest a specialized, regulated localization mechanism.
- This finding highlights distinct trafficking properties of D2 autoreceptors in dopaminergic neurons compared to other neuronal populations and receptor types.
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