Dopamine responsiveness is regulated by targeted sorting of D2 receptors

Selena E. Bartlett; Johan Enquist; Frederic W. Hopf; Josephine H. Lee; Fredrik Gladher; Viktor Kharazia; Maria Waldhoer; William S. Mailliard; Randall Armstrong; Antonello Bonci; Jennifer L. Whistler

doi:10.1073/pnas.0502418102

Dopamine responsiveness is regulated by targeted sorting of D2 receptors

Selena E. Bartlett, Johan Enquist, Frederic W. Hopf, Josephine H. Lee, Fredrik Gladher, Viktor Kharazia, Maria Waldhoer, William S. Mailliard, Randall Armstrong, Antonello Bonci, Jennifer L. Whistler

Research output: Contribution to journal › Article › peer-review

141 Scopus citations

Abstract

Aberrant dopaminergic signaling is a critical determinant in multiple psychiatric disorders, and in many disease states, dopamine receptor number is altered. Here we identify a molecular mechanism that selectively targets D2 receptors for degradation after their activation by dopamine. The degradative fate of D2 receptors is determined by an interaction with G protein coupled receptor-associated sorting protein (GASP). As a consequence of this GASP interaction, D2 responses in rat brain fail to resensitize after agonist treatment. Disruption of the D2-GASP interaction facilitates recovery of D2 responses, suggesting that modulation of the D2-GASP interaction is important for the functional down-regulation of D2 receptors.

Original language	English (US)
Pages (from-to)	11521-11526
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	102
Issue number	32
DOIs	https://doi.org/10.1073/pnas.0502418102
State	Published - Aug 9 2005
Externally published	Yes

Keywords

Degradation
Down-regulation
G protein-coupled receptor
Resensitization
Trafficking

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.0502418102

Cite this

Bartlett, S. E., Enquist, J., Hopf, F. W., Lee, J. H., Gladher, F., Kharazia, V., Waldhoer, M., Mailliard, W. S., Armstrong, R., Bonci, A., & Whistler, J. L. (2005). Dopamine responsiveness is regulated by targeted sorting of D2 receptors. Proceedings of the National Academy of Sciences of the United States of America, 102(32), 11521-11526. https://doi.org/10.1073/pnas.0502418102

Bartlett, SE, Enquist, J, Hopf, FW, Lee, JH, Gladher, F, Kharazia, V, Waldhoer, M, Mailliard, WS, Armstrong, R, Bonci, A & Whistler, JL 2005, 'Dopamine responsiveness is regulated by targeted sorting of D2 receptors', Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 32, pp. 11521-11526. https://doi.org/10.1073/pnas.0502418102

@article{aa7a9f3bb8934bffae3401a85ec58f62,

title = "Dopamine responsiveness is regulated by targeted sorting of D2 receptors",

abstract = "Aberrant dopaminergic signaling is a critical determinant in multiple psychiatric disorders, and in many disease states, dopamine receptor number is altered. Here we identify a molecular mechanism that selectively targets D2 receptors for degradation after their activation by dopamine. The degradative fate of D2 receptors is determined by an interaction with G protein coupled receptor-associated sorting protein (GASP). As a consequence of this GASP interaction, D2 responses in rat brain fail to resensitize after agonist treatment. Disruption of the D2-GASP interaction facilitates recovery of D2 responses, suggesting that modulation of the D2-GASP interaction is important for the functional down-regulation of D2 receptors.",

keywords = "Degradation, Down-regulation, G protein-coupled receptor, Resensitization, Trafficking",

author = "Bartlett, {Selena E.} and Johan Enquist and Hopf, {Frederic W.} and Lee, {Josephine H.} and Fredrik Gladher and Viktor Kharazia and Maria Waldhoer and Mailliard, {William S.} and Randall Armstrong and Antonello Bonci and Whistler, {Jennifer L.}",

year = "2005",

month = aug,

day = "9",

doi = "10.1073/pnas.0502418102",

language = "English (US)",

volume = "102",

pages = "11521--11526",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "32",

}

TY - JOUR

T1 - Dopamine responsiveness is regulated by targeted sorting of D2 receptors

AU - Bartlett, Selena E.

AU - Enquist, Johan

AU - Hopf, Frederic W.

AU - Lee, Josephine H.

AU - Gladher, Fredrik

AU - Kharazia, Viktor

AU - Waldhoer, Maria

AU - Mailliard, William S.

AU - Armstrong, Randall

AU - Bonci, Antonello

AU - Whistler, Jennifer L.

PY - 2005/8/9

Y1 - 2005/8/9

N2 - Aberrant dopaminergic signaling is a critical determinant in multiple psychiatric disorders, and in many disease states, dopamine receptor number is altered. Here we identify a molecular mechanism that selectively targets D2 receptors for degradation after their activation by dopamine. The degradative fate of D2 receptors is determined by an interaction with G protein coupled receptor-associated sorting protein (GASP). As a consequence of this GASP interaction, D2 responses in rat brain fail to resensitize after agonist treatment. Disruption of the D2-GASP interaction facilitates recovery of D2 responses, suggesting that modulation of the D2-GASP interaction is important for the functional down-regulation of D2 receptors.

AB - Aberrant dopaminergic signaling is a critical determinant in multiple psychiatric disorders, and in many disease states, dopamine receptor number is altered. Here we identify a molecular mechanism that selectively targets D2 receptors for degradation after their activation by dopamine. The degradative fate of D2 receptors is determined by an interaction with G protein coupled receptor-associated sorting protein (GASP). As a consequence of this GASP interaction, D2 responses in rat brain fail to resensitize after agonist treatment. Disruption of the D2-GASP interaction facilitates recovery of D2 responses, suggesting that modulation of the D2-GASP interaction is important for the functional down-regulation of D2 receptors.

KW - Degradation

KW - Down-regulation

KW - G protein-coupled receptor

KW - Resensitization

KW - Trafficking

UR - http://www.scopus.com/inward/record.url?scp=23844437253&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23844437253&partnerID=8YFLogxK

U2 - 10.1073/pnas.0502418102

DO - 10.1073/pnas.0502418102

M3 - Article

C2 - 16049099

AN - SCOPUS:23844437253

SN - 0027-8424

VL - 102

SP - 11521

EP - 11526

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

IS - 32

ER -

Dopamine responsiveness is regulated by targeted sorting of D2 receptors

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this