Dopamine responsiveness is regulated by targeted sorting of D2 receptors
Dopamine responsiveness is regulated by targeted sorting of D2 receptors
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DOI：
10.1073/pnas.0502418102
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发表时间：
2005-08-09
影响因子：
11.1
通讯作者：
Whistler, JL
中科院分区：
文献类型：
--
作者：
Bartlett, SE;Enquist, J;Whistler, JL
多巴胺能信号异常是多种精神疾病的关键决定因素，在许多疾病状态下，多巴胺受体数量发生改变。在这里，我们确定了一种分子机制，选择性地靶向D2受体在多巴胺激活后降解。D2受体的降解命运是由与G蛋白偶联受体相关分选蛋白（GASP）的相互作用决定的。由于这种GASP相互作用的结果，D2反应在激动剂治疗后不能再致敏。D2- gasp相互作用的破坏有助于D2反应的恢复，这表明D2- gasp相互作用的调节对D2受体的功能下调很重要。
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.