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The 4 mammalian arrestins serve as almost universal regulators of the largest known family of signaling proteins, G-protein-coupled receptors (GPCRs). Arrestins terminate receptor interactions with G proteins, redirect the signaling to a variety of alternative pathways, and orchestrate receptor internalization and subsequent intracellular trafficking. The(More)
Arrestin proteins play a key role in desensitizing G-protein-coupled receptors and re-directing their signaling to alternative pathways. The precise timing of arrestin binding to the receptor and its subsequent dissociation is ensured by its exquisite selectivity for the activated phosphorylated form of the receptor. The interaction between arrestin and the(More)
We characterized the binding of [125I]epidepride to dopamine D2-like and D3-like receptors in tissue sections of human striatum. The competition for binding of [125I]epidepride by domperidone, quinpirole, and 7-hydroxy-N,N-di(1-propyl)-2-aminotetralin (7-OH-DPAT) was best fit by assuming one site in the caudate but two sites in nucleus accumbens. Guanosine(More)
In rod photoreceptors, arrestin localizes to the outer segment (OS) in the light and to the inner segment (IS) in the dark. Here, we demonstrate that redistribution of arrestin between these compartments can proceed in ATP-depleted photoreceptors. Translocation of transducin from the IS to the OS also does not require energy, but depletion of ATP or GTP(More)
The transcription factor cAMP response element-binding protein (CREB) within the nucleus accumbens (NAc) plays an important role in regulating mood. In rodents, increased CREB activity within the NAc produces depression-like signs including anhedonia, whereas disruption of CREB activity by expression of a dominant-negative CREB (mCREB, which acts as a CREB(More)
The dopamine D2 and D3 receptors are members of the D2 subfamily that includes the D2, D3 and D4 receptor. In the rat, the D3 receptor exhibits a distribution restricted to mesolimbic regions with little overlap with the D2 receptor. Receptor binding and nonisotopic in situ hybridization were used to study the distribution of the D3 receptors and neurons(More)
The extent of nigrostriatal denervation is presumed to play a role in the genesis of levodopa-induced dyskinesia. Yet some parkinsonian patients who have been treated over a long period do not develop dyskinesia, raising the possibility that the pattern of denervation is as important as the extent of lesioning as a risk factor. Here we study the extent and(More)
In vertebrates, the arrestins are a family of four proteins that regulate the signaling and trafficking of hundreds of different G-protein-coupled receptors (GPCRs). Arrestin homologs are also found in insects, protochordates and nematodes. Fungi and protists have related proteins but do not have true arrestins. Structural information is available only for(More)
Parkinson's disease is caused primarily by degeneration of brain dopaminergic neurons in the substantia nigra and the consequent deficit of dopamine in the striatum. Dopamine replacement therapy with the dopamine precursor l-dopa is the mainstay of current treatment. After several years, however, the patients develop l-dopa-induced dyskinesia, or abnormal(More)
Accumulating evidence of G-protein-coupled receptor (GPCR) oligomerization on the one hand and perfect functionality of monomeric receptors on the other creates an impression of controversy. However, the GPCR superfamily is extremely diverse, both structurally and functionally. The life cycle of each receptor includes many stages: synthesis, quality control(More)