Inhibition of cortical astrocyte differentiation by Hes6 requires amino- and carboxy-terminal motifs important for dimerization and phosphorylation.

Abstract:

:Hairy/Enhancer of split (Hes) 6 is a basic helix-loop-helix protein that interacts with the transcriptional co-repressor, Groucho, and antagonizes the neural functions of the Notch pathway. More specifically, mouse Hes6 regulates cerebral corticogenesis by promoting neurogenesis and suppressing astrocyte differentiation. The molecular mechanisms underlying the anti-astrogenic function of Hes6 are poorly defined. Here we describe studies aimed at testing whether Hes6 inhibits astrocyte differentiation by antagonizing the transcription repression activity of Notch-activated Hes family members like Hes1. It is reported that Hes6 preferentially forms homodimers. Heterodimerization with Hes1 is antagonized in part by a conserved N-terminal patch of negatively charged residues. Mutation of this motif enhances heterodimerization with Hes1 and increases Hes6 ability to antagonize Hes1-mediated transcriptional repression. However, this mutation does not increase, but instead decreases, the anti-astrogenic activity of Hes6. It is shown further that Hes6 harbors a second conserved sequence, a C-terminal SPXXSP motif. This sequence is phosphorylated by the mitogen activated protein kinase pathway and its mutation disrupts the anti-astrogenic activity of Hes6 without affecting its ability to suppress Hes1. Together, these observations suggest that Hes6 homodimers regulate astrocyte differentiation through mechanisms that depend on the phosphorylation of Hes6 C-terminal domain but are independent of its ability to suppress Hes1-mediated transcriptional repression.

journal_name

J Neurochem

authors

Belanger-Jasmin S,Llamosas E,Tang Y,Joachim K,Osiceanu AM,Jhas S,Stifani S

doi

10.1111/j.1471-4159.2007.04902.x

subject

Has Abstract

pub_date

2007-12-01 00:00:00

pages

2022-34

issue

5

eissn

0022-3042

issn

1471-4159

pii

JNC4902

journal_volume

103

pub_type

杂志文章
  • Myelin basic protein-specific RNA levels in interleukin-2-stimulated oligodendrocytes.

    abstract::In the immune system, T- and B-cell proliferation, as well as B-cell immunoglobulin secretion, is induced by interleukin-2 (IL-2), a T-cell-derived lymphokine. IL-2 also influences the growth of glial cells, specifically, the proliferation and maturation of oligodendrocytes. Studies were conducted to investigate furth...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1987.tb10020.x

    authors: Benveniste EN,Herman PK,Whitaker JN

    更新日期:1987-10-01 00:00:00

  • Thermodynamics of agonist and antagonist interaction with the strychnine-sensitive glycine receptor.

    abstract::The thermodynamic parameters associated with the interactions of agonists and antagonists with glycine receptors in rat spinal cord membranes were determined. The binding of the antagonist [3H]strychnine and the inhibition of strychnine binding by 11 different glycinergic ligands were examined at temperatures between ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1989.tb07256.x

    authors: Ruiz-Gómez A,García-Calvo M,Vázquez J,Marvizón JC,Valdivieso F,Mayor F Jr

    更新日期:1989-06-01 00:00:00

  • Structural stabilization of CNS synapses during postnatal development in rat cortex.

    abstract::CNS synapses are produced rapidly upon pre- and post-synaptic recruitment. However, their composition is known to change during development and we reasoned that this may be reflected in the gross biochemical properties of synapses. We found synaptic structure in adult cortical synaptosomes to be resistant to digestion...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2006.03898.x

    authors: Khaing ZZ,Fidler L,Nandy N,Phillips GR

    更新日期:2006-07-01 00:00:00

  • Stimulatory effect of ascorbic acid on norepinephrine biosynthesis in digitonin-permeabilized adrenal medullary chromaffin cells.

    abstract::The regulatory role of ascorbic acid in norepinephrine biosynthesis was studied using digitonin-permeabilized chromaffin cells. When permeabilized chromaffin cells were incubated with [3H]3,4-dihydroxyphenylethylamine ([3H]dopamine) in calcium-free medium, the amounts of radioactive dopamine and norepinephrine measure...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1986.tb13060.x

    authors: Morita K,Levine M,Pollard HB

    更新日期:1986-03-01 00:00:00

  • Parameters related to lipid metabolism as markers of myelination in mouse brain.

    abstract::Myelination, during both normal development and with respect to disorders of myelination, is commonly studied by morphological and/or biochemical techniques that assay as their end-points the extent of myelination. The rate of myelination is potentially a more useful parameter, but it is difficult and time-consuming t...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2001.00015.x

    authors: Muse ED,Jurevics H,Toews AD,Matsushima GK,Morell P

    更新日期:2001-01-01 00:00:00

  • Amino acid neurotransmitters in nucleus tractus solitarius: an in vivo microdialysis study.

    abstract::Amino acid neurotransmitters in the nucleus tractus solitarius (NTS) are thought to play a key role in the mediation of visceral reflexes and glutamate has been proposed as the neurotransmitter of visceral afferent nerves projecting to this region. The present studies sought to characterize the use of in vivo microdia...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1993.tb07446.x

    authors: Sved AF,Curtis JT

    更新日期:1993-12-01 00:00:00

  • Multiple defects in the activity of adenylate cyclase from the Drosophila memory mutant rutabaga.

    abstract::Adenylate cyclase in homogenates of Drosophila melanogaster is heterogeneous with respect to its affinity toward MgATP and its subcellular distribution. Km values for MgATP range, under similar assay conditions, from approximately 10(-5) M to approximately 10(-3) M, depending on the body region and on the subcellular ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1985.tb03996.x

    authors: Dudai Y,Zvi S

    更新日期:1985-08-01 00:00:00

  • An astrocyte-specific enhancer of the aquaporin-4 gene functions through a consensus sequence of POU transcription factors in concert with multiple upstream elements.

    abstract::Aquaporin-4, a predominant water channel in the brain, is specifically expressed in astrocyte endfeet and plays a central role in water homeostasis, neuronal activity, and cell migration in the brain. It has two dominant isoforms called M1 and M23, whose mRNA is driven by distinct promoters located upstream of exons 0...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2012.07652.x

    authors: Abe Y,Ikeshima-Kataoka H,Goda W,Niikura T,Yasui M

    更新日期:2012-03-01 00:00:00

  • Emerging functions of the calpain superfamily of cysteine proteases in neuroendocrine secretory pathways.

    abstract::The first calpain protease was discovered over 40 years ago now, yet despite the vast amount of literature that has subsequently emerged detailing their involvement in the pathophysiology of a variety of human diseases, it is only in the last decade that calpain-mediated actions along the secretory pathway have begun ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章,评审

    doi:10.1111/j.1471-4159.2007.04815.x

    authors: Evans JS,Turner MD

    更新日期:2007-11-01 00:00:00

  • Differential effects of delta- and mu-opioid receptor antagonists on the amphetamine-induced increase in extracellular dopamine in striatum and nucleus accumbens.

    abstract::The specific opioid receptor antagonist naloxone attenuates the behavioral and neurochemical effects of amphetamine. Furthermore, the amphetamine-induced increase in locomotor activity is attenuated by intracisternally administered naltrindole, a selective delta-opioid receptor antagonist, but not by the irreversible ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1996.67062292.x

    authors: Schad CA,Justice JB Jr,Holtzman SG

    更新日期:1996-12-01 00:00:00

  • Sodium phenylbutyrate prolongs survival and regulates expression of anti-apoptotic genes in transgenic amyotrophic lateral sclerosis mice.

    abstract::Multiple molecular defects trigger cell death in amyotrophic lateral sclerosis (ALS). Among these, altered transcriptional activity may perturb many cellular functions, leading to a cascade of secondary pathological effects. We showed that pharmacological treatment, using the histone deacetylase inhibitor sodium pheny...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2005.03077.x

    authors: Ryu H,Smith K,Camelo SI,Carreras I,Lee J,Iglesias AH,Dangond F,Cormier KA,Cudkowicz ME,Brown RH Jr,Ferrante RJ

    更新日期:2005-06-01 00:00:00

  • Antisense strategy unravels a dopamine receptor distinct from the D2 subtype, uncoupled with adenylyl cyclase, inhibiting prolactin release from rat pituitary cells.

    abstract::The antisense strategy was used to unravel the functional contribution of the mRNAs encoding dopamine (DA) receptors to the multiple transduction mechanisms operated by DA in rat pituitary cells. An antisense oligonucleotide was designed to recognize seven nucleotides upstream and 11 nucleotides downstream from the in...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1994.62041260.x

    authors: Valerio A,Alberici A,Tinti C,Spano P,Memo M

    更新日期:1994-04-01 00:00:00

  • Molecular cloning of a novel member of the HSP110 family of genes, ischemia-responsive protein 94 kDa (irp94), expressed in rat brain after transient forebrain ischemia.

    abstract::To identify genes induced by transient forebrain ischemia, we used the mRNA differential display technique in the four-vessel occlusion model in rats. Some genes were identified as candidates that encode ischemia-responsive protein, and one of them was cloned as ischemia-responsive protein 94 kDa (irp94) from the rat ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1999.721544.x

    authors: Yagita Y,Kitagawa K,Taguchi A,Ohtsuki T,Kuwabara K,Mabuchi T,Matsumoto M,Yanagihara T,Hori M

    更新日期:1999-04-01 00:00:00

  • Cellular expression, developmental regulation, and phylogenic conservation of PEA-15, the astrocytic major phosphoprotein and protein kinase C substrate.

    abstract::PEA-15 has recently been identified as a major phosphoprotein in astrocytes and an endogenous substrate for protein kinase C. This 15-kDa protein exists under three molecular forms, an unphosphorylated form, N, and two phosphorylated forms, Pa and Pb. Antisera were raised against synthetic peptides corresponding to th...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1995.64031016.x

    authors: Danziger N,Yokoyama M,Jay T,Cordier J,Glowinski J,Chneiweiss H

    更新日期:1995-03-01 00:00:00

  • Mitochondrial carbonic anhydrase in the nervous system: expression in neuronal and glial cells.

    abstract::Carbonic anhydrase (CA) V is a mitochondrial enzyme that has been reported in several tissues of the gastrointestinal tract. In liver, it participates in ureagenesis and gluconeogenesis by providing bicarbonate ions for two other mitochondrial enzymes: carbamyl phosphate synthetase I and pyruvate carboxylase. This stu...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2000.0752212.x

    authors: Ghandour MS,Parkkila AK,Parkkila S,Waheed A,Sly WS

    更新日期:2000-11-01 00:00:00

  • Pyrrolines as prodrugs of gamma-aminobutyric acid analogues.

    abstract::delta 1-Pyrroline, 5-methyl-delta 1-pyrroline, and 5,5-dimethyl-delta 1-pyrroline have been identified as substances metabolized to gamma-aminobutyric acid (GABA), 4-aminopentanoic acid (methylGABA), and 4-amino-4-methylpentanoic acid (dimethylGABA), respectively. An enzyme system residing in the soluble fraction of r...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1982.tb05348.x

    authors: Callery PS,Geelhaar LA,Nayar MS,Stogniew M,Rao KG

    更新日期:1982-04-01 00:00:00

  • Effects of muscarinic agonists and depolarizing agents on inositol monophosphate accumulation in the rabbit vagus nerve.

    abstract::The effects of muscarinic agonists and depolarizing agents on inositol phospholipid hydrolysis in the rabbit vagus nerve were assessed by the measurement of [3H]inositol monophosphate production in nerves that had been preincubated with [3H]inositol. After 1 h of drug action, carbachol, oxotremorine, and arecoline inc...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1992.tb09392.x

    authors: Sierro CD,Vitus J,Dunant Y

    更新日期:1992-08-01 00:00:00

  • Glutamate-dependent transcriptional regulation of GLAST: role of PKC.

    abstract::The Na+-dependent glutamate/aspartate transporter GLAST plays a major role in the removal of glutamate from the synaptic cleft. Short-term, as well as long-term changes in transporter activity are triggered by glutamate. An important locus of regulation is the density of transporter molecules present at the plasma mem...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2004.02706.x

    authors: López-Bayghen E,Ortega A

    更新日期:2004-10-01 00:00:00

  • Fatty acid acylation of rat brain myelin proteolipid protein in vitro: identification of the lipid donor.

    abstract::The immediate acyl chain donor for fatty acid esterification of proteolipid protein (PLP) was identified in an in vitro system. Rat brain total membranes, after removal of crude nuclear and mitochondrial fractions, were incubated with radioactive acyl donors, extracted with chloroform/methanol, and analyzed by sodium ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1986.tb13013.x

    authors: Bizzozero OA,Lees MB

    更新日期:1986-02-01 00:00:00

  • Human amylin induces "apoptotic" pattern of gene expression concomitant with cortical neuronal apoptosis.

    abstract::Amylin forms large beta-pleated neurotoxic oligomers but shows only 38% sequence similarity to A beta. As patterns of gene expression during neuronal apoptosis appear stimulus and cell type specific, we compared the pattern of amylin-induced gene expression in rat cortical neurons with that shown previously to be indu...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1998.71020506.x

    authors: Tucker HM,Rydel RE,Wright S,Estus S

    更新日期:1998-08-01 00:00:00

  • Phosphorylase alpha and labile metabolites during anoxia: correlation to membrane fluxes of K+ and Ca2+.

    abstract::The objective of the present study was to explore mechanisms responsible for activation of ion conductances in the initial phases of brain ischemia, particularly for the early release of K+ that precedes massive cell depolarization, and rapid downhill fluxes of K+, Na+, Cl-, and Ca2+. As it has been speculated that a ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1990.tb04957.x

    authors: Folbergrová J,Minamisawa H,Ekholm A,Siesjö BK

    更新日期:1990-11-01 00:00:00

  • Role of glycine in the N-methyl-D-aspartate-mediated neuronal cytotoxicity.

    abstract::Current evidence indicates that glutamate acting via the N-methyl-D-aspartate (NMDA) receptor/ion channel complex plays a major role in the neuronal degeneration associated with a variety of neurological disorders. In this report the role of glycine in NMDA neurotoxicity was examined. We demonstrate that NMDA-mediated...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1990.tb02329.x

    authors: Patel J,Zinkand WC,Thompson C,Keith R,Salama A

    更新日期:1990-03-01 00:00:00

  • Astrocyte activation in vivo during graded photic stimulation.

    abstract::Astrocytes have important roles in control of extracellular environment, de novo synthesis of neurotransmitters, and regulation of neurotransmission and blood flow. All of these functions require energy, suggesting that astrocytic metabolism should rise and fall with changes in neuronal activity and that brain imaging...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2007.04859.x

    authors: Dienel GA,Schmidt KC,Cruz NF

    更新日期:2007-11-01 00:00:00

  • High serotonin and 5-hydroxyindoleacetic acid levels in limbic brain regions in a rat model of depression: normalization by chronic antidepressant treatment.

    abstract::Although alterations in serotonin levels and neurotransmission are associated with depressive disorders and effective antidepressant therapy, the exact cause of these disorders and the mode of action of antidepressant drugs are poorly understood. In a genetic rat model of depression [Flinders sensitive line (FSL) rats...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1997.69062477.x

    authors: Zangen A,Overstreet DH,Yadid G

    更新日期:1997-12-01 00:00:00

  • Acetylcholine turnover and compartmentation in rat brain synaptosomes.

    abstract::The turnover of acetylcholine (ACh) in rat brain synaptosomes and its compartmentation in the labile bound and stable bound pools were investigated. The P(2) fraction from rat brain was subjected to three sequential incubations, each terminated by centrifugation followed by determination of ACh concentrations by gas c...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1981.tb00423.x

    authors: Jope RS

    更新日期:1981-05-01 00:00:00

  • Hexose translocation across the blood-brain interface: configurational aspects.

    abstract::The translocation of intravenously administered tritiated 3-O-methyl-D-glucopyranose (3-OMG) into brain has been studied in an intact nephrectomized rat preparation by infusing a series of hexoses into one internal carotid artery. 3-OMG rapidly penetrated into brain with peak concentrations, attained 5-8 min after inj...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1968.tb10333.x

    authors: Bidder TG

    更新日期:1968-08-01 00:00:00

  • Involvement of kappa/dynorphin system in the development of tolerance to nicotine-induced antinociception.

    abstract::The aim of the present study was to explore the possible role of kappa/dynorphin system in the development of tolerance to nicotine antinociception in mice. First, we observed that kappa-opioid receptor (KOP-r) participates in the acute spinal antinociception produced by nicotine (3 and 5 mg/kg, s.c.) since the pre-tr...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2008.05247.x

    authors: Galeote L,Maldonado R,Berrendero F

    更新日期:2008-05-01 00:00:00

  • Nature of the autofluorescent material in cerebrocortical necrosis.

    abstract::A distinctive autofluorescence under ultraviolet light has been observed in the cerebral cortex of young ruminants suffering from cerebrocortical necrosis. The fluorescence is intimately connected with structural elements of the brain and cannot be extracted into solvents by normal procedures. The work presented here ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1981.tb04497.x

    authors: Edwin EE,Jackman R

    更新日期:1981-10-01 00:00:00

  • Enhanced hippocampal F2-isoprostane formation following kainate-induced seizures.

    abstract::We attempted to obtain evidence for the occurrence of oxidant injury following seizure activity by measuring hippocampal F2-isoprostanes (F2-IsoPs), a reliable marker of free radical-induced lipid peroxidation. Formation of F2-IsoPs esterified in hippocampal phospholipids was correlated with hippocampal neuronal loss ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2001.00659.x

    authors: Patel M,Liang LP,Roberts LJ 2nd

    更新日期:2001-12-01 00:00:00

  • Selective presynaptic cholinergic neurotoxicity following intrahippocampal AF64A injection in rats.

    abstract::Compound AF64A, ethylcholine mustard aziridinium ion (0.4-8 nmol) was stereotaxically administered into rat dorsal hippocampus, and neurochemical changes were determined 5 days later. AF64A treatment, over an almost 10-fold dose range, resulted in a significant (up to 70%) decline in choline acetyltransferase activity...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1983.tb11836.x

    authors: Mantione CR,Zigmond MJ,Fisher A,Hanin I

    更新日期:1983-07-01 00:00:00