多巴胺反应性由D2受体的靶向分选调节。
Dopamine responsiveness is regulated by targeted sorting of D2 receptors.
作者信息
Bartlett Selena E, Enquist Johan, Hopf Frederic W, Lee Josephine H, Gladher Fredrik, Kharazia Viktor, Waldhoer Maria, Mailliard William S, Armstrong Randall, Bonci Antonello, Whistler Jennifer L
机构信息
Ernest Gallo Clinic and Research Center, University of California, San Francisco, CA 94608, USA.
出版信息
Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11521-6. doi: 10.1073/pnas.0502418102. Epub 2005 Jul 27.
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.
摘要
异常的多巴胺能信号传导是多种精神疾病的关键决定因素，在许多疾病状态下，多巴胺受体数量会发生改变。在此，我们确定了一种分子机制，该机制在多巴胺激活D2受体后选择性地靶向其进行降解。D2受体的降解命运由与G蛋白偶联受体相关分选蛋白（GASP）的相互作用决定。由于这种GASP相互作用，大鼠脑中D2受体的反应在激动剂处理后无法再敏化。破坏D2-GASP相互作用有助于D2反应的恢复，这表明调节D2-GASP相互作用对于D2受体的功能下调很重要。
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