Interaction with dopamine D2 receptor enhances expression of transient receptor potential channel 1 at the cell surface.
Receptor signaling is mediated by direct protein interaction with various types of cytoskeletal, adapter, effector, and additional receptor molecules. In brain tissue and in cultured neurons, activation of dopamine D2 receptors (D2Rs) has been found to impact cellular calcium signaling. Using a yeast two-hybrid approach, we have uncovered a direct physical interaction between the D2R and the transient receptor potential channel (TRPC) subtypes 1, 4 and 5. The TRPC/D2R interaction was further validated by GST-pulldown assays and coimmunoprecipitation from mammalian brain. Ultrastructural analysis of TRPC1 and D2R expression indicates colocalization of the two proteins within the cell body and dendrites of cortical neurons. In cultured cells, expression of D2Rs was found to increase expression of TRPC1 at the cell surface by 50%. These findings shed new light on the constituents of the D2R signalplex, and support the involvement of D2Rs in cellular calcium signaling pathways via a novel link to TRPC channels.
Hannan
Meredith A
MA
Department of Pharmacology, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Kabbani
Nadine
N
Paspalas
Constantinos D
CD
Levenson
Robert
R
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019921:Biotinylation; D002460:Cell Line; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000737:chemistry / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D050052:TRPC Cation Channels / Q000737:chemistry / Q000378:metabolism*
D017448:Receptors, Dopamine D2; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1