Dopamine responsiveness is regulated by targeted sorting of D2 receptors
(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.
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/227121
- author
- organization
- publishing date
- 2005
- 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}}, }