Dopamine Tone Regulates D1 Receptor Trafficking and Delivery in Striatal Neurons in Dopamine Transporter-Deficient Mice

In vivo, G protein-coupled receptors (GPCR) for neurotransmitters undergo complex intracellular trafficking that contribute to regulate their abundance at the cell surface. Here, we report a previously undescribed alteration in the subcellular localization of D1 dopamine receptor (D1R) that occurs i...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2000-02, Vol.97 (4), p.1879-1884
Main Authors: Dumartin, Brigitte, Jaber, Mohamed, Gonon, Francois, Caron, Marc G., Giros, Bruno, Bloch, Bertrand
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Biology
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell membranes
Cellular immunity
Cytoplasm
Dendrites
Dopamine - metabolism
Dopamine Plasma Membrane Transport Proteins
Electrochemistry
Endoplasmic reticulum
Endoplasmic Reticulum - metabolism
Golgi apparatus
Golgi Apparatus - metabolism
GTP-Binding Proteins - metabolism
Immunohistochemistry
Membrane Glycoproteins
Membrane Transport Proteins
Mice
Mice, Knockout
Microscopy, Electron
Mutation
Nerve Tissue Proteins
Neurology
Neurons
Neurotransmitters
Oxidopamine - pharmacology
Plasma cells
Prosencephalon - drug effects
Prosencephalon - ultrastructure
protein trafficking
Receptors
Receptors, Dopamine D1 - metabolism
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Summary:In vivo, G protein-coupled receptors (GPCR) for neurotransmitters undergo complex intracellular trafficking that contribute to regulate their abundance at the cell surface. Here, we report a previously undescribed alteration in the subcellular localization of D1 dopamine receptor (D1R) that occurs in vivo in striatal dopaminoceptive neurons in response to chronic and constitutive hyperdopaminergia. Indeed, in mice lacking the dopamine transporter, D1R is in abnormally low abundance at the plasma membrane of cell bodies and dendrites and is largely accumulated in rough endoplasmic reticulum and Golgi apparatus. Decrease of striatal extracellular dopamine concentration with 6-hydroxydopamine (6-OHDA) in heterozygous mice restores delivery of the receptor from the cytoplasm to the plasma membrane in cell bodies. These results demonstrate that, in vivo, in the central nervous system, the storage in cytoplasmic compartments involved in synthesis and the membrane delivery contribute to regulate GPCR availability and abundance at the surface of the neurons under control of the neurotransmitter tone. Such regulation may contribute to modulate receptivity of neurons to their endogenous ligands and related exogenous drugs.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.97.4.1879