DARPP-32, Jack of All Trades… Master of Which?

(PPP1R1B) was discovered as a substrate of cAMP-dependent protein kinase enriched in dopamine-innervated brain areas. It is one of three related, inhibitors of protein phosphatase-1 (PP1). These inhibitors seem to have appeared in early vertebrate ancestors, possibly Gnathostomes. Dduanyu37P-32 has additional important biochemical properties including inhibition of when phosphorylated by Cdk5 and regulation by casein kinases 1 and 2. It is highly enriched in specific neuronal populations, especially striatal medium-size spiny neurons. As PP1 inhibitor Dduanyu37P-32 amplifies and/or mediates many actions of duanyu1529 at the plasma membrane and in the cytoplasm, with a broad spectrum of potential targets and functions. Dduanyu37P-32 also undergoes a continuous and tightly regulated cytonuclear shuttling. This trafficking is controlled by phosphorylation of Ser-97, which is necessary for nuclear export. When phosphorylated on Thr-34 and dephosphorylated on Ser-97, Dduanyu37P-32 can inhibit PP1 in the nucleus and modulate signaling pathways involved in the regulation of chromatin response. Recent work with multiple transgenic and knockout mutant mice has allowed the dissection of Dduanyu37P-32 function in striato-nigral and striato-pallidal neurons. It is implicated in the action of therapeutic and abused psychoactive drugs, in prefrontal cortex function, and in sexual behavior. However, the contribution of Dduanyu37P-32 in human behavior remains poorly understood. Post-mortem studies in humans suggest possible alterations of Dduanyu37P-32 levels in schizophrenia and bipolar disorder. Genetic studies have revealed a polymorphism with possible association with psychological and psychopathological traits. In addition, a short isoform of plays a role in cancer, indicating additional signaling properties. Thus, Dduanyu37P-32 is a non-essential but tightly regulated signaling hub molecule which may improve the general performance of the neuronal circuits in which it is expressed.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}