DARPP—32的结构,功能及其调节机制

DARPP-32是一种多巴胺（DA）和cAMP调节的磷蛋白，存在于所有接受DA能投射的神经元中，在中枢神经系统的分布与DAD1受体的分布非常一致。DA通过D1受体使DARPP-32第34位苏氨酸磷酸化，磷酸化DARPP-32成为蛋白磷酸酶1（PP-1）的强效抑制剂，在两个不同位点与PP-1相互作用，从而抑制PP-1活性。DARPP-32／PP-1级联反应在调节，如钙通道、电压依赖性钠通道、Na＋,K＋-ATPase和NMDANR1受体的功能等神经元兴奋性过程中起重要作用。DA对DARPP—32的磷酸化状态有双向调节作用，其他许多神经递质亦可调节其磷酸化状态。

DARPP-32: Structure, function and the underlying regulatory mechanism

DARPP-32, a dopamine (DA) and cAMP regulated phosphoprotein of apparentMr 32 000Pa,is enriched in all neurons that receive a dopaminergic input and have a restrictedregional distribution that paralleled the distribution of D1 receptors.Dopamine, by acting on theD1 receptors,leads to the phosphorylation of DARPP-32 on a signal threonine residue (Thr34),converting it into a potent inhibitor of protein phosphatase 1(PP-1). Phospho-DARPP-32 exerts its inhibition on PP-1 activity by interaction between DARPP-32 and PP-1 at two distinctsites.DARPP-32/PP-1 cascade has a significant role in the regulation of neuronal excitability suchas the functions of calcium channels, voltage dependant sodium channel, Na ,K -ATPase andNMDA receptor NR1 subunit.DA exerts a bidirectional control on the state of phosphorylation ofDARPP-32 and other many neurotransmitters also regulate its phosphorylation and dephosphorylation.