Dopamine D2 and D3 receptors are linked to the actin cytoskeleton via interaction with filamin A

Proceedings of the National Academy of Sciences of the United States of America
R LinRobert Levenson

Abstract

We have used a yeast two-hybrid approach to uncover protein interactions involving the D2-like subfamily of dopamine receptors. Using the third intracellular loop of the D2S and D3 dopamine receptors as bait to screen a human brain cDNA library, we identified filamin A (FLN-A) as a protein that interacts with both the D2 and D3 subtypes. The interaction with FLN-A was specific for the D2 and D3 receptors and was independently confirmed in pull-down and coimmunoprecipitation experiments. Deletion mapping localized the dopamine receptor-FLN-A interaction to the N-terminal segment of the D2 and D3 dopamine receptors and to repeat 19 of FLN-A. In cultures of dissociated rat striatum, FLN-A and D2 receptors colocalized throughout neuronal somata and processes as well as in astrocytes. Expression of D2 dopamine receptors in FLN-A-deficient M2 melanoma cells resulted in predominant intracellular localization of the D2 receptors, whereas in FLN-A-reconstituted cells, the D2 receptor was predominantly localized at the plasma membrane. These results suggest that FLN-A may be required for proper cell surface expression of the D2 dopamine receptors. Association of D2 and D3 dopamine receptors with FLN-A provides a mechanism whereby specifi...Continue Reading

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Citations

Mar 25, 2010·Neuroscience Bulletin·Ming-Lei GuoJohn Q Wang
Nov 6, 2010·Archives of Pharmacal Research·Dong Im ChoKyeong-Man Kim
Jun 1, 2005·Biochemical and Biophysical Research Communications·Jae-Hyo ParkKwonseop Kim
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Sep 12, 2003·Trends in Pharmacological Sciences·Clare BergsonMichael S Lidow
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Jan 28, 2004·Annual Review of Pharmacology and Toxicology·Christopher M TanLee E Limbird
Jan 20, 2007·The Journal of Clinical Investigation·William R ThelinSharon L Milgram
Feb 8, 2013·Cell & Bioscience·Jingyin YueZhiyuan Shen
Sep 3, 2010·PloS One·Laura MinsaasAnna M Aragay
Sep 8, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jingping ZhangVolney Sheen
Dec 24, 2002·Proceedings of the National Academy of Sciences of the United States of America·Phil Ok KohMichael S Lidow
Jul 15, 2009·Cellular and Molecular Life Sciences : CMLS·Ryan T Kendall, Louis M Luttrell
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