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Protein Kinase Cβ Coordinates Dopamine Transporter and Dopamine Autoreceptor Signaling
Author(s) -
Luderman Kathryn Diane,
Chen Rong,
Gereau Robert W,
Gnegy Margaret E
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1083.4
Subject(s) - protein kinase c , autoreceptor , dopamine , exocytosis , dopamine transporter , internalization , microbiology and biotechnology , chemistry , dopamine plasma membrane transport proteins , receptor , g protein coupled receptor , agonist , signal transduction , medicine , endocrinology , biology , biochemistry , dopaminergic , membrane
Dopamine (DA) neurons contain dopamine transporters (DAT) and presynaptic D2 dopamine receptors (D2DR), which inhibit DA exocytosis and increase DAT trafficking to the plasmalemmal membrane upon agonist stimulation. Using PKCβ −/− mice, we find that protein kinase Cβ (PKCβ) regulates constitutive and stimulated DAT trafficking plus D2DR activities: PKCβ reduces D2DR‐controlled DA exocytosis, but enhances the ability of D2DRs to increase DAT trafficking. Because PKCβ phosphorylates D2DR, which may increase receptor internalization, we hypothesize that lack of PKCβ will enhance D2DR surface localization. Radioligand binding and immunoflorescence labeling experiments were performed to determine surface localization of D2DR and DAT following treatment with the specific PKCβ inhibitor LY379196. Inhibition of PKCβ significantly increased the surface localization of D2DR in both assays but had no effect on DAT surface levels. Our results indicate that PKCβ facilitates D2DR and DAT coupling. In the absence of PKCβ activity, the coupling between D2DR and DAT is lost, as seen by the discoordination between D2DR and DAT. This work was supported by NIH grants DA011697, DA007267, and GM07767.