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Dopamine responsiveness is regulated by targeted sorting of D2 receptors

Bartlett, S E ; Enquist, Johan LU ; Hopf, F W ; Lee, J H ; Gladher, F ; Kharazia, V ; Waldhoer, M ; Mailliard, W S ; Armstrong, R and Bonci, A , et al. (2005) In Proceedings of the National Academy of Sciences 102(32). p.11521-11526
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.
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
down-regulation, G protein-coupled receptor, trafficking, resensitization, degradation
in
Proceedings of the National Academy of Sciences
volume
102
issue
32
pages
11521 - 11526
publisher
National Academy of Sciences
external identifiers
  • wos:000231253400070
  • scopus:23844437253
ISSN
1091-6490
DOI
10.1073/pnas.0502418102
language
English
LU publication?
yes
id
d3d239fa-8527-4ae4-a8a1-6c5fd2189b06 (old id 227121)
date added to LUP
2016-04-01 11:32:51
date last changed
2022-01-26 06:57:58
@article{d3d239fa-8527-4ae4-a8a1-6c5fd2189b06,
  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.}},
  author       = {{Bartlett, S E and Enquist, Johan and Hopf, F W and Lee, J H and Gladher, F and Kharazia, V and Waldhoer, M and Mailliard, W S and Armstrong, R and Bonci, A and Whistler, J L}},
  issn         = {{1091-6490}},
  keywords     = {{down-regulation; G protein-coupled receptor; trafficking; resensitization; degradation}},
  language     = {{eng}},
  number       = {{32}},
  pages        = {{11521--11526}},
  publisher    = {{National Academy of Sciences}},
  series       = {{Proceedings of the National Academy of Sciences}},
  title        = {{Dopamine responsiveness is regulated by targeted sorting of D2 receptors}},
  url          = {{http://dx.doi.org/10.1073/pnas.0502418102}},
  doi          = {{10.1073/pnas.0502418102}},
  volume       = {{102}},
  year         = {{2005}},
}