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

Ridwan Lin, Kelly Karpa, Nadine Kabbani, Patricia Goldman-Rakic, Robert Levenson

Research output: Contribution to journalArticle

156 Citations (Scopus)

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 specific dopamine receptor subtypes may be functionally linked to downstream signaling components via the actin cytoskeleton.

Original languageEnglish (US)
Pages (from-to)5258-5263
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number9
DOIs
StatePublished - Apr 24 2001

Fingerprint

Filamins
Dopamine D3 Receptors
Dopamine D2 Receptors
Actin Cytoskeleton
Dopamine Receptors
Carisoprodol
Gene Library
Astrocytes
Melanoma
Proteins
Yeasts
Cell Membrane

All Science Journal Classification (ASJC) codes

  • General

Cite this

@article{ecf8df9ecb764d808174c1713899f636,
title = "Dopamine D2 and D3 receptors are linked to the actin cytoskeleton via interaction with filamin A",
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 specific dopamine receptor subtypes may be functionally linked to downstream signaling components via the actin cytoskeleton.",
author = "Ridwan Lin and Kelly Karpa and Nadine Kabbani and Patricia Goldman-Rakic and Robert Levenson",
year = "2001",
month = "4",
day = "24",
doi = "10.1073/pnas.011538198",
language = "English (US)",
volume = "98",
pages = "5258--5263",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "9",

}

Dopamine D2 and D3 receptors are linked to the actin cytoskeleton via interaction with filamin A. / Lin, Ridwan; Karpa, Kelly; Kabbani, Nadine; Goldman-Rakic, Patricia; Levenson, Robert.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 9, 24.04.2001, p. 5258-5263.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Dopamine D2 and D3 receptors are linked to the actin cytoskeleton via interaction with filamin A

AU - Lin, Ridwan

AU - Karpa, Kelly

AU - Kabbani, Nadine

AU - Goldman-Rakic, Patricia

AU - Levenson, Robert

PY - 2001/4/24

Y1 - 2001/4/24

N2 - 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 specific dopamine receptor subtypes may be functionally linked to downstream signaling components via the actin cytoskeleton.

AB - 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 specific dopamine receptor subtypes may be functionally linked to downstream signaling components via the actin cytoskeleton.

UR - http://www.scopus.com/inward/record.url?scp=0035942279&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035942279&partnerID=8YFLogxK

U2 - 10.1073/pnas.011538198

DO - 10.1073/pnas.011538198

M3 - Article

C2 - 11320256

AN - SCOPUS:0035942279

VL - 98

SP - 5258

EP - 5263

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 9

ER -