Abstract:
:Dopamine plays an important role in the etiology of schizophrenia, and D2 class dopamine receptors are the best-established target of antipsychotic drugs. Here we show that D2 class-receptor-mediated Akt regulation involves the formation of signaling complexes containing beta-arrestin 2, PP2A, and Akt. beta-arrestin 2 deficiency in mice results in reduction of dopamine-dependent behaviors, loss of Akt regulation by dopamine in the striatum, and disruption of the dopamine-dependent interaction of Akt with its negative regulator, protein phosphatase 2A. Importantly, canonical cAMP-mediated dopamine-receptor signaling is not inhibited in the absence of beta-arrestin 2. These results demonstrate that, apart from its classical function in receptor desensitization, beta-arrestin 2 also acts as a signaling intermediate through a kinase/phosphatase scaffold. Furthermore, this function of beta-arrestin 2 is important for the expression of dopamine-associated behaviors, thus implicating beta-arrestin 2 as a positive mediator of dopaminergic synaptic transmission and a potential pharmacological target for dopamine-related psychiatric disorders.
journal_name
Celljournal_title
Cellauthors
Beaulieu JM,Sotnikova TD,Marion S,Lefkowitz RJ,Gainetdinov RR,Caron MGdoi
10.1016/j.cell.2005.05.012subject
Has Abstractpub_date
2005-07-29 00:00:00pages
261-73issue
2eissn
0092-8674issn
1097-4172pii
S0092-8674(05)00457-5journal_volume
122pub_type
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