Disease relevance of Ppp1r1b

• These observations indicate that the tanycytic population of the arcuate nucleus undergoes important modifications during aging, which include cell loss, impairment in the intracellular signalling cascade linked to DARPP-32, and hypertrophy [1].
• Lack of change in striatal DARPP-32 levels following nigrostriatal dopaminergic lesions in animals and in parkinsonian syndromes in man [2].
• Postmortem studies, carried out on brains obtained shortly after death, from patients with Parkinson disease, or from patients with progressive supranuclear palsy, showed that the levels of striatal DARPP-32 were not different from controls [2].
• RESULTS: The [32P]phosphate incorporation of DARPP-32 was reduced in vitro following ischemia [3].
• Western blot analysis showed that phosphorylated DARPP-32 at Thr75 increased in concentration after formalin hyperalgesia, with this effect reduced by roscovitine administration [4].

Psychiatry related information on Ppp1r1b

• Linear regression analysis showed that measurements of striatal DARPP-32 optical density and striatal [123I]IBZM uptake of the lesioned side were highly correlated (r2=0.83; P<0.001) whereas correlation with locomotor activity was less tight (r2=0.23; P<0.05; amphetamine-induced rotational behavior was not significantly correlated) [5].
• DARPP-32-rich zones in grafts of lateral ganglionic eminence govern the extent of functional recovery in skilled paw reaching in an animal model of Huntington's disease [6].

High impact information on Ppp1r1b

• One mechanism involves control of PP-1 catalytic activity by DARPP-32, a dopamine- and cAMP-regulated phosphoprotein highly enriched in neostriatum [7].
• Protein phosphatase 1 modulation of neostriatal AMPA channels: regulation by DARPP-32 and spinophilin [7].
• The phosphoprotein DARPP-32 mediates cAMP-dependent potentiation of striatal N-methyl-D-aspartate responses [8].
• When oocytes were coinjected with rat hippocampal poly(A)+ mRNA plus complementary RNA coding for DARPP-32, NMDA responses were potentiated after stimulation of PKA [8].
• We report here that CCK-8S abolishes cAMP-dependent phosphorylation of a dopamine- and cAMP-regulated 32-kDa phosphoprotein (DARPP-32) in striatal neurons [9].

Chemical compound and disease context of Ppp1r1b

• CONCLUSION: Dopamine depletion reduced the DARPP-32 phosphorylation in vivo following ischemia, and protected DARPP-32 immunoreactivity and mRNA expression level against the reduction induced by ischemia [3].

Biological context of Ppp1r1b

• Conversely, in morphine-sensitized rats, no apparent modifications in DARPP-32 phosphorylation pattern were observed [10].
• Overexpressed TRE-853-82Q protein led to proteolytic release of N-terminal htt fragments, nuclear aggregation, and a striatal dysfunction as revealed by decrease of DARPP-32 staining but absence of NeuN down-regulation [11].
• DARPP-32 first appears in the rat brain at day 14 of gestation, in the anlage of the primary olfactory cortex and the caudate nucleus [12].
• Exposure of cultures to high concentrations of L-DOPA induced the following changes: cell death in nigral and striatal neurons, aggregation of neurofilaments and focal axonal swellings, abnormal expression of DARPP-32, and activation of astroglia and microglial cells [13].
• These results establish an assay for in vivo studies of postsynaptic responses involving second messengers in the DA system and provide direct in vivo evidence for the hypothesis that stimulation of D1 receptors increases the phosphorylation of DARPP-32, as well as several other proteins [14].

Anatomical context of Ppp1r1b

• DARPP-32 (dopamine and 3',5'-cyclic adenosine monophosphate-regulated neuronal phosphoprotein) is essential for the maintenance of thyroid differentiation [15].
• Cocaine-sensitized rats showed increased phosphorylation of dopamine- and cyclic AMP-regulated phosphoprotein Mr 32 kDa (DARPP-32) at threonine-75 (Thr75) and decreased DARPP-32 phosphorylation at Thr34, in the caudate-putamen (CPu) and nucleus accumbens (NAc) 7 days after sensitization assessment [10].
• Concomitantly, a decrease in the amount of PP-2A and DARPP-32 phosphorylation at Thr34, but an increase in phosphorylation of DARPP-32/Thr75, was observed in the ventral striatum of sensitized rats [16].
• DARPP-32-like immunoreactivity in AII amacrine cells of rat retina [17].
• In the present study, we investigated the nitric oxide (NO)/cGMP pathway for its ability to regulate the state of phosphorylation of DARPP-32 in slices of rat substantia nigra [18].

Associations of Ppp1r1b with chemical compounds

• One notable exception is DARPP-32 (dopamine and cAMP-regulated neuronal phosphoprotein, molecular mass, 32 kDa), a third messenger that integrates multiple signaling pathways in the brain [15].
• The cyclin-dependent kinase Cdk5 and DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of Mr 32 kDa)-dependent signaling have been implicated in the regulation of dopaminergic neurotransmission after chronic cocaine treatment [16].
• We further immunoquantified DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, mw 32,000) and phosphothreonine-DARPP-32, which can be dephosphorylated at threonine sites by CaN [19].
• Decreased calcineurin and increased phosphothreonine-DARPP-32 in the striatum of rats behaviorally sensitized to methamphetamine [19].
• DARPP-32 was phosphorylated on threonine-34 in these slices by sodium nitroprusside (SNP), an NO donor [18].

Regulatory relationships of Ppp1r1b

• The data are consistent with a model in which GABA increases the phosphorylation state of DARPP-32 by inhibiting dephosphorylation of the protein by the calcium/calmodulin-dependent protein phosphatase, calcineurin [20].
• Interestingly, the cellular expression of glutamate decarboxylase messenger RNA was considerably higher in the non-DARPP-32 expressing regions than that in the DARPP-32 messenger RNA-rich areas, where it approximated that of the intact striatum [21].
• These results suggest that the neuronal diversity of the adult striatum may derive both from the lateral ganglionic eminence, providing DARPP-32-expressing projection neurons as well as somatostatin-containing interneurons, and the early stage medial ganglionic eminence specifically contributing the cholinergic interneurons [22].
• Tyrosine hydroxylase (TH) and dopamine- and cyclic adenosine 3':5'-monophosphate-regulated phosphoprotein (DARPP 32) immunocytochemistry showed mesencephalic and striatal graft survival in most animals [23].

Other interactions of Ppp1r1b

• Consistently, DARPP-32 reexpression in ras-transformed cells results in reactivation of the otherwise silent thyroglobulin and thyroperoxidase promoter [15].
• Here we show that DARPP-32 expression is targeted by TSH and IGF-I in thyrocytes [15].
• Both early and delayed DARPP-32, GluR1 and NR1 phosphorylation changes were prevented by a dopamine D1 receptor antagonist administration [24].
• Cdk5 and phosphorylation of its downstream target, DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of M(r) 32 kDa), were investigated by Western blot analysis [4].
• In addition to the nuclei mentioned above, DARPP-32-containing cell bodies also appear over the intervening period in the olfactory nucleus, nucleus accumbens, central amygdaloid nucleus, lateral funiculus, and the choroid plexus and ependymal layers of the third, fourth, and lateral ventricles and the Sylvian aqueduct [12].

Analytical, diagnostic and therapeutic context of Ppp1r1b

• They contained striatum-like patches with neurons expressing many of the neurochemicals characteristic of striatum (ACh, ChAT, calbindin-D28KD, met-enkephalin, and dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein-32,000 or DARPP-32), and these patches were surrounded by graft tissue expressing few of these striatal markers [25].
• Immunohistochemistry using DARPP-32 as striatal marker and tyrosinhydroxylase as marker for nigral neurons was performed for correlation analysis of imaging and histological parameters [26].
• We here report the pre- and postnatal distributions of DARPP-32 in the kidney as demonstrated by immunoblotting and immunohistochemistry [27].
• Northern blot analysis indicates that the steady-state level of DARPP-32 mRNA in striatum is also unchanged by these treatments [28].
• The regional and cellular ontogeny of the mRNA encoding the dopamine- and cAMP-regulated phosphoprotein, DARPP-32, has been studied in rat striatum by quantitative in situ hybridization histochemistry [29].

References