title: Trafficking properties of the D5 dopamine receptor.
abstract: Dopamine receptors are important for diverse biological functions and are important pharmacological targets in human medicine. Signal transduction from the dopamine receptors is controlled at many levels, including by the process of receptor trafficking. Little is known regarding the endocytic and postendocytic trafficking properties of the D5 dopamine receptor. Here, we show that endocytosis of the D5 receptor can be achieved both homologously, through direct receptor activation by agonist, and also heterologously, due to independent activation of protein kinase C (PKC). In contrast, the D1 receptor is endocytosed only in response to agonist but not PKC activation. We have identified the residue in the third intracellular loop of the D5 receptor that is both necessary for PKC-mediated endocytosis of the D5 receptor and sufficient to induce PKC-mediated endocytosis when introduced to the D1 receptor. In addition, we show that endocytosis of D5 through both pathways is dependent on clathrin and dynamin but that only agonist-induced endocytosis engages β-arrestin 2. Together, these data show that the D5 receptor shows a trafficking profile distinct from that of any of the other dopamine receptors.
authors.affiliation: Department of Neurology, Ernest Gallo Clinic & Research Center, University of California, San Francisco, Emeryville, CA 94608, USA.
authors.forename: Dawn
authors.initials: D
authors.lastname: Thompson
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Whistler
mesh_terms: D019390:Arrestins / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation; D057809:HEK293 Cells; D006801:Humans; D020033:Protein Isoforms / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology*; D034622:RNA Interference; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism; D050641:Receptors, Dopamine D5 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
chemical_list: C000605254:ARRB2 protein, human; D019390:Arrestins; D002966:Clathrin; D020033:Protein Isoforms; D017447:Receptors, Dopamine D1; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D050641:Receptors, Dopamine D5; D011493:Protein Kinase C; D034281:Dynamins; D013755:Tetradecanoylphorbol Acetate; D004298:Dopamine