Abstract:
:Dystrobrevin binding protein-1 (dysbindin-1), a candidate gene for schizophrenia, modulates cognition, synaptic plasticity and frontocortical circuitry and interacts with glutamatergic and dopaminergic transmission. Loss of dysbindin-1 modifies cellular trafficking of dopamine (DA) D2 receptors to increase cell surface expression, but its influence upon signaling has never been characterized. Further, the effects of dysbindin-1 upon closely related D3 receptors remain unexplored. Hence, we examined the impact of dysbindin-1 (isoform A) co-expression on the localization and coupling of human D2L and D3 receptors stably expressed in Chinese hamster ovary or SH-SY5Y cells lacking endogenous dysbindin-1. Dysbindin-1 co-transfection decreased cell surface expression of both D3 and D2L receptors. Further, while their affinity for DA was unchanged, dysbindin-1 reduced the magnitude and potency of DA-induced adenylate cylase recruitment/cAMP production. Dysbindin-1 also blunted the amplitude of DA-induced phosphorylation of ERK1/2 and Akt at both D2L and D3 receptors without, in contrast to cAMP, affecting the potency of DA. Interference with calveolin/clathrin-mediated processes of internalization prevented the modification by dysbindin-1 of ERK1/2 and adenylyl cyclase stimulation at D2L and D3 receptors. Finally, underpinning the specificity of the influence of dysbindin-1 on D2L and D3 receptors, dysbindin-1 did not modify recruitment of adenylyl cyclase by D1 receptors. These observations demonstrate that dysbindin-1 influences cell surface expression of D3 in addition to D2L receptors, and that it modulates activation of their signaling pathways. Accordingly, both a deficiency and an excess of dysbindin-1 may be disruptive for dopaminergic transmission, supporting its link to schizophrenia and other CNS disorders. Dysbindin-1, a candidate gene for schizophrenia, alters D2 receptors cell surface expression. We demonstrate that dysbindin-1 expression also influences cell surface levels of D3 receptors. Further, Dysbindin-1 reduces DA-induced adenylate cylase recruitment/cAMP production and modifies major signaling pathways (Akt and extracellular signal-regulated kinases1/2 (ERK1/2)) of both D2 and D3 receptors. Dysbindin-1 modulates thus D2 and D3 receptor signaling, supporting a link to schizophrenia.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Schmieg N,Rocchi C,Romeo S,Maggio R,Millan MJ,Mannoury la Cour Cdoi
10.1111/jnc.13501subject
Has Abstractpub_date
2016-03-01 00:00:00pages
1037-51issue
5eissn
0022-3042issn
1471-4159journal_volume
136pub_type
杂志文章abstract::Several mechanisms are thought to be involved in the progressive decline in neurons of the substantia nigra pars compacta (SNpc) that leads to Parkinson's disease (PD). Neurotoxin 6-hydroxydopamine (6-OHDA), which induces parkinsonian symptoms in experimental animals, is thought to be formed endogenously in patients w...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2002.00952.x
更新日期:2002-07-01 00:00:00
abstract::The long-term regulation of tyrosine hydroxylase (TH) by serotonin has been studied with cultures of newborn rat locus ceruleus explants. The presence of serotonin in the culture medium for a 24-h period was followed by an inhibition of TH activity in the explants. This effect lasted several days, with a maximal effec...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1987.tb00945.x
更新日期:1987-09-01 00:00:00
abstract::Increase in oxidative stress has been postulated to play an important role in the pathogenesis of a number of neurodegenerative diseases including Alzheimer's disease. There is evidence for involvement of amyloid-beta peptide (Abeta) in mediating the oxidative damage to neurons. Despite yet unknown mechanism, Abeta ap...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2008.05347.x
更新日期:2008-07-01 00:00:00
abstract::Deposit of beta-amyloid protein (A beta) in Alzheimer's disease brain may contribute to the associated neurodegeneration. We have studied the neurotoxicity of A beta in primary cultures of murine cortical neurons, with the aim of identifying pharmacologic ways of attenuating the injury. Exposure of cultures to A beta ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1994.62010372.x
更新日期:1994-01-01 00:00:00
abstract::Expression of rat brain gamma-aminobutyric acid type A (GABA(A)) receptors in Xenopus laevis oocytes can be achieved by injection of the oocytes with synaptosomes. This approach has now been applied to evaluate changes in the function of nigral GABA(A) receptors after degeneration of the striatonigral GABAergic pathwa...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1998.70062539.x
更新日期:1998-06-01 00:00:00
abstract::The neurotoxic effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was tested on mice lacking the dopamine (DA) transporter (DAT-/- mice). Striatal tissue DA content and glial fibrillary acidic protein (GFAP) mRNA expression were assessed as markers of MPTP neurotoxicity. MPTP (30 mg/kg, s.c., b.i.d.) produc...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1997.69031322.x
更新日期:1997-09-01 00:00:00
abstract::Glia maturation factor-beta, a protein found in the brains of all vertebrates thus far examined, appears to play a role in the differentiation, maintenance, and regeneration of the nervous system. Using oligonucleotide probes based on the sequences of three tryptic peptides derived from bovine glia maturation factor-b...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1991.tb03777.x
更新日期:1991-08-01 00:00:00
abstract::The Cys-loop receptor family consists of nicotinic acetylcholine receptors (nAChR), glycine receptor, GABA-A and some other receptors. They fulfill a plethora of functions, whereas their malfunctioning is associated with many diseases. All three domains - extracellular ligand-binding, membrane and cytoplasmic - of the...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
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更新日期:2011-03-01 00:00:00
abstract::Cell aggregation is one of several environmental cues that influence the expression of neurotransmitter phenotype during development. The expression of the catecholaminergic phenotype is increased in rat pheochromocytoma cells cultured at high density. In the present study we have investigated whether this cell densit...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1994.62030844.x
更新日期:1994-03-01 00:00:00
abstract::Plasma osmolality and the levels of water, taurine, and total amino nitrogen (detected as ninhydrin-positive substances) have been measured in the cerebral cortices of nonpregnant and 19-day pregnant Wistar rats. Plasma osmolality fell by 11 mosmol/kg during pregnancy. Brain water content remained unaltered, but level...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1989.tb07328.x
更新日期:1989-07-01 00:00:00
abstract::We studied the formation of early endosomes in differentiating oligodendrocytes and type-2 astrocytes, which are derived from common precursor cells in rat neonates, using fluorescent analogues of lactosylceramide (LacCer) and sulfatide labeled with 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene++ +-3-pentano...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1999.0731375.x
更新日期:1999-10-01 00:00:00
abstract::Somatostatin (SS) and neuropeptide Y (NPY) are coproduced in a subpopulation of neurons that are selectively resistant to NMDA neurotoxicity. We have previously reported that quinolinic acid (QUIN), an NMDA receptor agonist, augments SS mRNA in cultured fetal rat cortical neurons. This study examines coregulation of S...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1995.65030998.x
更新日期:1995-09-01 00:00:00
abstract::Significant progress has been made in the identification of intrinsic and extrinsic factors involved in the development of nervous system. It is remarkable that the establishment and maintenance of the asymmetrical architecture of a neuron is coordinated by a limited repertoire of signalling machineries. However, the ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1111/j.1471-4159.2006.04372.x
更新日期:2007-05-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1989.tb08524.x
更新日期:1989-11-01 00:00:00
abstract::Genomic and cDNA clones encoding the rat D1 receptor were isolated and sequenced. Comparison of the D1 receptor cDNA and genomic sequences revealed that the rat D1 receptor gene is organized into two exons separated by a small intron in the 5' untranslated region of its mRNA. The transcription start site is located 86...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1992.tb11023.x
更新日期:1992-11-01 00:00:00
abstract::Stabilized microtubules are required for neuronal morphogenesis and migration. However, the underlying mechanism is not fully understood. In this study, we demonstrate that myosin X (Myo10), which is composed of full-length myosin X (fMyo10) and headless myosin X (hMyo10), is important for axon development. fMyo10 is ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.13238
更新日期:2015-10-01 00:00:00
abstract::We have tested the hypothesis that exocytosis is a possible export route for calcium from bovine adrenal medullary cells. After prelabelling cells in primary tissue culture with 45Ca, evoked 45Ca export and catecholamine secretion show the same time course, a similar fraction of the total pool of 45Ca and catecholamin...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1989.tb07352.x
更新日期:1989-08-01 00:00:00
abstract::Transmitter release at high probability phasic synapses of crayfish neuromuscular junctions depresses by over 50% in 60 min when stimulated at 0.2 Hz. Inhibition of the protein phosphatase calcineurin by intracellular pre-synaptic injection of autoinhibitory peptide inhibited low-frequency depression (LFD) and resulte...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1985.tb05530.x
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1988.tb01181.x
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:2010-10-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1987.tb05591.x
更新日期:1987-03-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2007.04783.x
更新日期:2007-11-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1988.tb02489.x
更新日期:1988-06-01 00:00:00
abstract::Members of the protein kinase D (PKD) family of serine/threonine kinases are known to exert diverse roles in neuronal stress responses. Here, we show the transient activation and nuclear translocation of endogenous PKD upon oxidative stress induced by H2 O2 treatment in primary neuronal cultures. Using pharmacological...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.14131
更新日期:2017-09-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2003.01885.x
更新日期:2003-07-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1991.tb02071.x
更新日期:1991-05-01 00:00:00
abstract::Previous studies from this laboratory have shown that synthesis of GT3, the precursor of c series gangliosides, occurs in proximal Golgi compartments, as has been shown for the synthesis of GM3 and GD3, the precursors of a and b series gangliosides, respectively. In this work we studied whether the synthesis of GM3, G...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1996.67041393.x
更新日期:1996-10-01 00:00:00
abstract::Glutathione (GSH) and GSH-related enzymes constitute the most important defense system that protects cells from free radical, radiotherapy, and chemotherapy attacks. In this study, we aim to explore the potential role and regulatory mechanism of the GSH redox cycle in drug resistance in glioblastoma multiforme (GBM) c...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.14250
更新日期:2018-01-01 00:00:00
abstract::Induction of the prodynorphin gene occurs in a tissue-specific manner following different physiological stimuli. Using electrophoretic mobility shift assays, we studied the relative activity of the five major regulatory sites in the rat prodynorphin promoter. Prodynorphin cyclic AMP-responsive element 2 (DynCRE2), Dyn...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1998.70030914.x
更新日期:1998-03-01 00:00:00