Dopamine tone regulates D1 receptor trafficking and delivery in striatal neurons in dopamine transporter-deficient mice

摘要

ID vivo, G protein-coupled receptors (GPCR) for neurotransmitters undergo complex intracellular trafficking that contribute to regu- late their abundance at the cell surface. Here, we report a previ- ously undescribed alteration in the subcellular localization of D1 dopamine receptor (D1R) that occurs in vivo in striatal dopamino- ceptive neurons in response to chronic and constitutive hyperdo- paminergia. Indeed, in mice lacking the dopamine transporter, D1 R is in abnormally low abundance at the plasma membrane of cell bodies and dendrites and is largely accumulated in rough endo- plasmic reticulum and Golgi apparatus. Decrease of striatal extra- cellular 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 modu- late receptivity of neurons to their endogenous ligands and related exogenous drugs.