Arrestin-3-assisted activation of JNK3 mediates dopaminergic behavioral and signaling plasticity in vivo.
Arrestin-3-assisted activation of JNK3 mediates dopaminergic behavioral and signaling plasticity in vivo.
复制标题
Arrestin-3 辅助的 JNK3 激活介导体内多巴胺能行为和信号可塑性。
DOI：
10.1101/2023.10.27.564447
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Gurevich,EugeniaV
中科院分区：
文献类型：
--
作者：
Ahmed,MohamedR;Zheng,Chen;Dunning,JefferyL;Ahmed,MohamedS;Ge,Connie;SandersPair,F;Gurevich,VsevolodV;Gurevich,EugeniaV
In rodents with unilateral ablation of the substantia nigra neurons supplying dopamine to the striatum, chronic treatment with the dopamine precursor L-DOPA or dopamine agonists induces a progressive increase of behavioral responses, a process known as behavioral sensitization. The sensitization is blunted in arrestin-3 knockout mice. Using virus-mediated gene delivery to the dopamine-depleted striatum of arrestin-3 knockout mice, we found that the restoration of arrestin-3 fully rescued behavioral sensitization, whereas its mutant defective in JNK activation did not. A 25-residue arrestin-3-derived peptide that facilitates JNK3 activation in cells, expressed ubiquitously or selectively in the direct pathway striatal neurons, fully rescued sensitization, whereas an inactive homologous arrestin-2-derived peptide did not. Behavioral rescue was accompanied by the restoration of JNK3 activity and of JNK-dependent phosphorylation of the transcription factor c-Jun in the dopamine-depleted striatum. Thus, arrestin-3-dependent JNK3 activation in direct pathway neurons is a critical element of the molecular mechanism underlying sensitization.
