Genomes and Genes
Gene Symbol: DARPP 32
Description: protein phosphatase 1, regulatory (inhibitor) subunit 1B
Alias: AU040756, DARPP-32, Darpp32, protein phosphatase 1 regulatory subunit 1B, dopamine- and cAMP-regulated neuronal phosphoprotein
Products: DARPP 32
- Toresson H, Campbell K. A role for Gsh1 in the developing striatum and olfactory bulb of Gsh2 mutant mice. Development. 2001;128:4769-80 pubmed
- Toresson H, Mata De Urquiza A, Fagerstrom C, Perlmann T, Campbell K. Retinoids are produced by glia in the lateral ganglionic eminence and regulate striatal neuron differentiation. Development. 1999;126:1317-26 pubmed..These findings, therefore, strongly support the notion that local retinoid signalling within the lateral ganglionic eminence regulates striatal neuron differentiation. ..
- Bogush A, Pedrini S, Pelta Heller J, Chan T, Yang Q, Mao Z, et al. AKT and CDK5/p35 mediate brain-derived neurotrophic factor induction of DARPP-32 in medium size spiny neurons in vitro. J Biol Chem. 2007;282:7352-9 pubmed..These data support the presence of multiple signal transduction pathways mediating expression of DARPP-32 in vitro, including a novel, important pathway via by which PI3K regulates the contribution of cdk5/p35. ..
- Anderson S, Qiu M, Bulfone A, Eisenstat D, Meneses J, Pedersen R, et al. Mutations of the homeobox genes Dlx-1 and Dlx-2 disrupt the striatal subventricular zone and differentiation of late born striatal neurons. Neuron. 1997;19:27-37 pubmed..Several lines of evidence suggest that mutations in Dlx-1 and Dlx-2 produce abnormalities in the development of the striatal subventricular zone and in the differentiation of striatal matrix neurons. ..
- Nishi A, Watanabe Y, Higashi H, Tanaka M, Nairn A, Greengard P. Glutamate regulation of DARPP-32 phosphorylation in neostriatal neurons involves activation of multiple signaling cascades. Proc Natl Acad Sci U S A. 2005;102:1199-204 pubmed
- Waclaw R, Wang B, Pei Z, Ehrman L, Campbell K. Distinct temporal requirements for the homeobox gene Gsx2 in specifying striatal and olfactory bulb neuronal fates. Neuron. 2009;63:451-65 pubmed publisher..These results demonstrate that Gsx2 specifies striatal projection neuron and olfactory bulb interneuron identity at distinct time points during telencephalic neurogenesis. ..
- Corbin J, Gaiano N, Machold R, Langston A, Fishell G. The Gsh2 homeodomain gene controls multiple aspects of telencephalic development. Development. 2000;127:5007-20 pubmed..Taken together, our data support a model in which Gsh2, in response to sonic hedgehog signaling, plays a crucial role in multiple aspects of telencephalic development. ..
- Nishi A, Kuroiwa M, Miller D, O Callaghan J, Bateup H, Shuto T, et al. Distinct roles of PDE4 and PDE10A in the regulation of cAMP/PKA signaling in the striatum. J Neurosci. 2008;28:10460-71 pubmed publisher..These data underscore the importance of individual brain-enriched cyclic-nucleotide PDE isoforms as therapeutic targets for neuropsychiatric and neurodegenerative disorders affecting dopamine neurotransmission. ..
- Stipanovich A, Valjent E, Matamales M, Nishi A, Ahn J, Maroteaux M, et al. A phosphatase cascade by which rewarding stimuli control nucleosomal response. Nature. 2008;453:879-84 pubmed publisher..Mutation of Ser 97 profoundly alters behavioural effects of drugs of abuse and decreases motivation for food, underlining the functional importance of this signalling cascade. ..
- Santini E, Feyder M, Gangarossa G, Bateup H, Greengard P, Fisone G. Dopamine- and cAMP-regulated phosphoprotein of 32-kDa (DARPP-32)-dependent activation of extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin complex 1 (mTORC1) signaling in experimental parkinsonism. J Biol Chem. 2012;287:27806-12 pubmed publisher..These studies demonstrate that, in D1R-expressing MSNs, l-DOPA-induced activation of ERK and mTORC1 requires DARPP-32 and indicates the importance of the cAMP/DARPP-32 signaling cascade in dyskinesia. ..
- Andersson M, Usiello A, Borgkvist A, Pozzi L, Dominguez C, Fienberg A, et al. Cannabinoid action depends on phosphorylation of dopamine- and cAMP-regulated phosphoprotein of 32 kDa at the protein kinase A site in striatal projection neurons. J Neurosci. 2005;25:8432-8 pubmed
- Heyser C, Fienberg A, Greengard P, Gold L. DARPP-32 knockout mice exhibit impaired reversal learning in a discriminated operant task. Brain Res. 2000;867:122-30 pubmed..These results provide evidence for a functional role of DARPP-32 in the mediation of processes underlying learning and memory. ..
- Chang M, Zhong F, Lavik A, Parys J, Berridge M, Distelhorst C. Feedback regulation mediated by Bcl-2 and DARPP-32 regulates inositol 1,4,5-trisphosphate receptor phosphorylation and promotes cell survival. Proc Natl Acad Sci U S A. 2014;111:1186-91 pubmed publisher..This feedback mechanism appears to be exploited by high levels of Bcl-2 in chronic lymphocytic leukemia cells, repressing B-cell receptor-induced Ca(2+) elevation and apoptosis. ..
- Wang B, Lufkin T, Rubenstein J. Dlx6 regulates molecular properties of the striatum and central nucleus of the amygdala. J Comp Neurol. 2011;519:2320-34 pubmed publisher..RNA expression array analysis of the E18.5 striatum was useful in identifying the transcription factors that are expressed in this tissue, but did not identify major changes in gene expression in the Dlx6(LacZ/LacZ) mutant. ..
- Sánchez N, Coura R, Engmann O, Marion Poll L, Longueville S, Herve D, et al. Haloperidol-induced Nur77 expression in striatopallidal neurons is under the control of protein phosphatase 1 regulation by DARPP-32. Neuropharmacology. 2014;79:559-66 pubmed publisher..Our results clarify the mechanisms of Nur77 induction by antipsychotic and its possible contribution to extrapyramidal effects. ..
- Precious S, Kelly C, Reddington A, Vinh N, Stickland R, Pekarik V, et al. FoxP1 marks medium spiny neurons from precursors to maturity and is required for their differentiation. Exp Neurol. 2016;282:9-18 pubmed publisher..We demonstrate the utility of FoxP1 to label MSNs in vitro and following neural transplantation, and show that FoxP1 is required for DARPP-32 positive MSN differentiation in vitro. ..
- Oeckl P, Hengerer B, Ferger B. G-protein coupled receptor 6 deficiency alters striatal dopamine and cAMP concentrations and reduces dyskinesia in a mouse model of Parkinson's disease. Exp Neurol. 2014;257:1-9 pubmed publisher..These findings could offer an opportunity for the treatment of Parkinson's disease beyond dopamine replacement. ..
- Lazenka M, Tomarchio A, Lichtman A, Greengard P, Flajolet M, Selley D, et al. Role of Dopamine Type 1 Receptors and Dopamine- and cAMP-Regulated Phosphoprotein Mr 32 kDa in Î”9-Tetrahydrocannabinol-Mediated Induction of Î”FosB in the Mouse Forebrain. J Pharmacol Exp Ther. 2015;354:316-27 pubmed publisher..These results indicate that D1Rs play a major role in THC-mediated Î”FosB induction in the forebrain, whereas the role of DARPP-32 in THC-mediated Î”FosB induction and modulation of motor activity appears to be more complex. ..
- Woodworth M, Greig L, Liu K, Ippolito G, Tucker H, Macklis J. Ctip1 Regulates the Balance between Specification of Distinct Projection Neuron Subtypes in Deep Cortical Layers. Cell Rep. 2016;15:999-1012 pubmed publisher..Therefore, Ctip1 couples subtype and area specification, enabling specific functional areas to organize precise ratios of appropriate output projections. ..
- Burk K, Mire E, Bellon A, Hocine M, Guillot J, Moraes F, et al. Post-endocytic sorting of Plexin-D1 controls signal transduction and development of axonal and vascular circuits. Nat Commun. 2017;8:14508 pubmed publisher..Thus, intracellular sorting steps that occur after receptor internalization by endocytosis provide a critical level of control of cellular responses to guidance signals. ..
- Liao W, Tsai H, Wang H, Chang J, Lu K, Wu H, et al. Modular patterning of structure and function of the striatum by retinoid receptor signaling. Proc Natl Acad Sci U S A. 2008;105:6765-70 pubmed publisher..RARbeta signaling thus plays a crucial role in setting up striatal compartments that may engage in neural circuits of psychomotor control. ..
- Westerlund M, Ran C, Borgkvist A, Sterky F, Lindqvist E, Lundströmer K, et al. Lrrk2 and alpha-synuclein are co-regulated in rodent striatum. Mol Cell Neurosci. 2008;39:586-91 pubmed publisher..Because striatal Lrrk2 and alpha-synuclein levels were not changed by dopamine depletion, we conclude that Lrrk2 and alpha-synuclein mRNA levels are possibly co-regulated, but they are not influenced by striatal dopamine levels. ..
- Mani S, Fienberg A, O Callaghan J, Snyder G, Allen P, Dash P, et al. Requirement for DARPP-32 in progesterone-facilitated sexual receptivity in female rats and mice. Science. 2000;287:1053-6 pubmed..P also enhanced phosphorylation of DARPP-32 on threonine 34 in the hypothalamus of mice. DARPP-32 activation is thus an obligatory step in progestin receptor regulation of sexual receptivity in rats and mice. ..
- Risinger F, Freeman P, Greengard P, Fienberg A. Motivational effects of ethanol in DARPP-32 knock-out mice. J Neurosci. 2001;21:340-8 pubmed..2% w/v) was subsequently added to the ethanol mixture, and responding was examined at 0, 5, 10, and 20% ethanol concentrations. Ethanol responding increased in both genotypes, although WT mice showed higher rates at all concentrations. ..
- Onn S, Fienberg A, Grace A. Dopamine modulation of membrane excitability in striatal spiny neurons is altered in DARPP-32 knockout mice. J Pharmacol Exp Ther. 2003;306:870-9 pubmed..In contrast, D2 agonist applied simultaneously with the D1 agonist only produced a reduction in excitability. This type of D1-dependent modulation was not present in slices from the DARPP-32 knockout mice. ..
- Tamura S, Morikawa Y, Iwanishi H, Hisaoka T, Senba E. Foxp1 gene expression in projection neurons of the mouse striatum. Neuroscience. 2004;124:261-7 pubmed..The expression pattern of Foxp1 mRNA suggests that Foxp1 may play a role in the development and formation of a circuit in the basal ganglia, which is involving the matrix neurons. ..
- Tang T, Bezprozvanny I. Dopamine receptor-mediated Ca(2+) signaling in striatal medium spiny neurons. J Biol Chem. 2004;279:42082-94 pubmed..Our results indicate that, following D1 class DAR activation, InsP(3) and cAMP signaling pathways converge on the type 1 InsP(3) receptor, resulting in Ca(2+) oscillations in MSN. ..
- Nishi A, Liu F, Matsuyama S, Hamada M, Higashi H, Nairn A, et al. Metabotropic mGlu5 receptors regulate adenosine A2A receptor signaling. Proc Natl Acad Sci U S A. 2003;100:1322-7 pubmed..The results demonstrate that mGlu5 receptors potentiate adenosine A(2A)DARPP-32 signaling by stimulating the adenosine A(2A) receptor-mediated formation of cAMP in an extracellular signal-regulated kinase-dependent manner. ..
- Li J, Duarte T, Kocabas A, Works M, McConnell S, Hynes M. Evidence for topographic guidance of dopaminergic axons by differential Netrin-1 expression in the striatum. Mol Cell Neurosci. 2014;61:85-96 pubmed publisher..Our results reveal novel actions for Netrin-1 and provide evidence for a mechanism through which DA axons can selectively innervate one of two terminal zones in the striatum but have free reign to arborize widely within a terminal zone. ..
- Bonito Oliva A, Pallottino S, Bertran Gonzalez J, Girault J, Valjent E, Fisone G. Haloperidol promotes mTORC1-dependent phosphorylation of ribosomal protein S6 via dopamine- and cAMP-regulated phosphoprotein of 32 kDa and inhibition of protein phosphatase-1. Neuropharmacology. 2013;72:197-203 pubmed publisher..They also indicate that this effect is exerted by suppressing dephosphorylation at Ser240/244, through PKA-dependent activation of DARPP-32 and inhibition of PP-1. ..
- Zhu H, Lee M, Guan F, Agatsuma S, Scott D, Fabrizio K, et al. DARPP-32 phosphorylation opposes the behavioral effects of nicotine. Biol Psychiatry. 2005;58:981-9 pubmed..DARPP-32 opposes the behavioral effects of nicotine possibly via concurrent phosphorylation at the two threonine sites. ..
- Molotkova N, Molotkov A, Duester G. Role of retinoic acid during forebrain development begins late when Raldh3 generates retinoic acid in the ventral subventricular zone. Dev Biol. 2007;303:601-10 pubmed..Our results suggest that the role of RA during forebrain development begins late when Raldh3 expression initiates in the ventral subventricular zone. ..
- Zhu S, Soutto M, Chen Z, Peng D, Romero Gallo J, Krishna U, et al. Helicobacter pylori-induced cell death is counteracted by NF-?B-mediated transcription of DARPP-32. Gut. 2017;66:761-762 pubmed publisher..pylori infection and activation of NF-?B provides a link between infection, inflammation and gastric tumourigenesis. ..
- Engmann O, Giralt A, Gervasi N, Marion Poll L, Gasmi L, Filhol O, et al. DARPP-32 interaction with adducin may mediate rapid environmental effects on striatal neurons. Nat Commun. 2015;6:10099 pubmed publisher..Our results suggest a molecular pathway by which environmental changes may rapidly alter responsiveness of striatal neurons involved in the reward system. ..
- Bonito Oliva A, SÃ¶dersten E, Spigolon G, Hu X, Hellysaz A, Falconi A, et al. Differential regulation of the phosphorylation of Trimethyl-lysine27 histone H3 at serine 28 in distinct populations of striatal projection neurons. Neuropharmacology. 2016;107:89-99 pubmed publisher..These results identify H3K27me3S28p as a potential mediator of the effects exerted by amphetamine and haloperidol, and suggest that these drugs may act by re-activating PcG repressed target genes. ..
- Lee M, Yu J, Kim J, Seo J, Park E, Kim C, et al. Alteration of synaptic activity-regulating genes underlying functional improvement by long-term exposure to an enriched environment in the adult brain. Neurorehabil Neural Repair. 2013;27:561-74 pubmed publisher..Western blotting confirmed that SLC6A3, DARPP32 (PPP1R1B), and P2RY12 were largely altered in a region-specific manner...
- Zhu S, Belkhiri A, El Rifai W. DARPP-32 increases interactions between epidermal growth factor receptor and ERBB3 to promote tumor resistance to gefitinib. Gastroenterology. 2011;141:1738-48.e1-2 pubmed publisher..DARPP-32 promotes resistance of gastric cancer cells to gefitinib by promoting interaction between EGFR and ERBB3 and activating phosphatidylinositol-3-kinase-AKT signaling. ..
- Molero A, Gokhan S, Gonzalez S, Feig J, Alexandre L, Mehler M. Impairment of developmental stem cell-mediated striatal neurogenesis and pluripotency genes in a knock-in model of Huntington's disease. Proc Natl Acad Sci U S A. 2009;106:21900-5 pubmed publisher..We propose that these HD-associated developmental abnormalities might compromise neuronal homeostasis and subsequently render MSNs more vulnerable to late life stressors. ..
- Chen L, Chatterjee M, Li J. The mouse homeobox gene Gbx2 is required for the development of cholinergic interneurons in the striatum. J Neurosci. 2010;30:14824-34 pubmed publisher..Together, our data demonstrate that Gbx2 is required for the development of striatal cholinergic interneurons, perhaps by regulating tangential migration of the striatal cholinergic precursors...
- McDowell K, Hutchinson A, Wong Goodrich S, Presby M, Su D, Rodriguiz R, et al. Reduced cortical BDNF expression and aberrant memory in Carf knock-out mice. J Neurosci. 2010;30:7453-65 pubmed publisher..Together, these data reveal novel roles for CaRF in the organization and/or function of neural circuits that underlie essential aspects of learning and memory. ..
- Onn S, Lin M, Liu J, Grace A. Dopamine and cyclic-AMP regulated phosphoprotein-32-dependent modulation of prefrontal cortical input and intercellular coupling in mouse accumbens spiny and aspiny neurons. Neuroscience. 2008;151:802-16 pubmed
- Chandwani S, Keilani S, Ortiz Virumbrales M, Morant A, Bezdecny S, Ehrlich M. Induction of DARPP-32 by brain-derived neurotrophic factor in striatal neurons in vitro is modified by histone deacetylase inhibitors and Nab2. PLoS ONE. 2013;8:e76842 pubmed publisher..In addition, overexpression of Nab2 induced DARPP-32. We conclude that histone deacetylase inhibitors inhibit the induction of Nab2 by BDNF, and thereby the relative induction of DARPP-32. ..
- Giesert F, Hofmann A, Bürger A, Zerle J, Kloos K, Hafen U, et al. Expression analysis of Lrrk1, Lrrk2 and Lrrk2 splice variants in mice. PLoS ONE. 2013;8:e63778 pubmed publisher..In order to identify the origin of these two splice variants, we also analysed primary neural cultures independently and found cell-specific expression patterns for these variants in microglia and astrocytes. ..
- Svenningsson P, Tzavara E, Liu F, Fienberg A, Nomikos G, Greengard P. DARPP-32 mediates serotonergic neurotransmission in the forebrain. Proc Natl Acad Sci U S A. 2002;99:3188-93 pubmed..Our data indicate that DARPP-32 is essential not only for dopaminergic but also for serotonergic neurotransmission. ..
- Colombo E, Collombat P, Colasante G, Bianchi M, Long J, Mansouri A, et al. Inactivation of Arx, the murine ortholog of the X-linked lissencephaly with ambiguous genitalia gene, leads to severe disorganization of the ventral telencephalon with impaired neuronal migration and differentiation. J Neurosci. 2007;27:4786-98 pubmed..Altogether, these results highlight the critical functions of Arx in promoting neural migration and regulating basal ganglia differentiation in mice, consistent with the phenotype of XLAG patients...
- Svenningsson P, Fienberg A, Allen P, Moine C, Lindskog M, Fisone G, et al. Dopamine D(1) receptor-induced gene transcription is modulated by DARPP-32. J Neurochem. 2000;75:248-57 pubmed..These results demonstrate an important involvement of DARPP-32 in dopamine receptor-mediated regulation of gene expression both in striatal neurons, which are enriched in DARPP-32, and in pallidal neurons, which do not contain DARPP-32. ..