Abstract：
:Endoplasmic reticulum (ER) stress occurs when protein folding or maturation is disrupted. A malfunction in the ER stress response can lead to cell death and has been observed in many neurological diseases. However, how the ER stress response is regulated in neuronal cells remains largely unclear. Here, we studied an E3 ubiquitin ligase named neural precursor cell expressed developmentally down-regulated protein 4-like (Nedd4-2). Nedd4-2 is highly expressed in the brain and has a high affinity toward ubiquitinating membrane-bound proteins. We first utilized unbiased proteomic profiling with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) of isolated membrane fractions from mouse whole brains to identify novel targets of Nedd4-2. Through this screen, we found that the expression and ubiquitination of ribosomal proteins are regulated by Nedd4-2 and we confirmed an association between Nedd4-2 and ribosomes through ribosome sedimentation and polysome profiling. Further, we utilized immunoprecipitation and western blotting to show that induction of ER stress promotes an association between Nedd4-2 and ribosomal proteins, which is mediated through dephosphorylation of Nedd4-2 at serine-342. This increased interaction between Nedd4-2 and ribosomal proteins in turn mediates ER stress-associated translational suppression. In summary, the results of this study demonstrate a novel regulatory mechanism underlying the ER stress response and a novel function of Nedd4-2 in translational control. Our findings may shed light on neurological diseases in which the ER stress response or the function of Nedd4-2 is dysregulated.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Eagleman DE,Zhu J,Liu DC,Seimetz J,Kalsotra A,Tsai NPdoi
10.1111/jnc.15219subject
Has Abstractpub_date
2020-10-16 00:00:00eissn
0022-3042issn
1471-4159pub_type
杂志文章abstract：:This paper proposes a tentative amino acid sequence of guinea pig myelin basic protein obtained by comparison of peptide fragments of the guinea pig and bovine proteins. Analyses of the tryptic peptides confirmed the known sequence differences in the NH2-terminal half of the molecule and showed that in the COOH-termin...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1984.tb06683.x
更新日期：1984-07-01 00:00:00
abstract：:Our results provide evidence that 6-hydroxydopamine induced, after auto-oxidation, toxic levels of hydrogen peroxide (H2O2) that caused bovine chromaffin cell toxicity and death. 6-Hydroxydopamine (6-OHDA) treatment markedly reduced, in a dose-response fashion, chromaffin cell viability. Cell death was accompanied by ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2003.01592.x
更新日期：2003-03-01 00:00:00
abstract：:Drebrin is a well-known side-binding protein of F-actin in the brain. Immunohistochemical data suggest that the peripheral parts of growing axons are enriched in the drebrin E isoform and mature axons are not. It has also been observed that drebrin E is concentrated in the growth cones of PC12 cells. These data strong...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2009.05993.x
更新日期：2009-04-01 00:00:00
abstract：:Membrane vesicles, showing a 21 +/- 2-fold enrichment in the activity of 5'-nucleotidase and a 11 +/- 4-fold enrichment in the activity of angiotensin-converting enzyme relative to homogenate, were prepared from the myenteric plexus-containing longitudinal muscle layer of guinea pig ileum. Incubation of the vesicles w...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1986.tb00690.x
更新日期：1986-09-01 00:00:00
abstract：:Disulfide-bridged S100b protein formation, aircatalyzed and induced by thiol/disulfide exchange, was studied under various ionic conditions. As native, physiological disulfide-bridged proteins are obtained easily from their reduced counterparts under appropriate redox conditions, this work was performed to determine w...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1990.tb03111.x
更新日期：1990-10-01 00:00:00
abstract：:To investigate if the prevention of disulfide bond formation affects the intracellular transport, sorting, and processing of a distinct set of neuroendocrine proteins in the regulated secretory pathway, we have treated Xenopus intermediate pituitaries with the thiol-reducing agent dithiothreitol. Pulse-chase incubatio...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.71010402.x
更新日期：1998-07-01 00:00:00
abstract：:We have developed a novel competitive method to select from a phage display library a single chain Fv which is able to mimic the alpha-bungarotoxin binding site of the muscle nicotinic receptor. The single chain Fv was selected from a large synthetic library using alpha-bungarotoxin-coated magnetic beads. Toxin-bound ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2001.00398.x
更新日期：2001-07-01 00:00:00
abstract：:The physiological function of the cellular prion protein (PrP(c)) is unclear. PrP(c) associates with lipid rafts, highly glycolipid-rich membrane domains containing a large variety of signaling molecules, e.g., sphingolipids (SL). In this study, we investigated possible connections between PrP(c) and sphingolipid-asso...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2008.05498.x
更新日期：2008-08-01 00:00:00
abstract：:Lysophosphatidic acid (LPA) is a potent lipid biomediator that is likely to have diverse roles in the brain. Thus, LPA-induced events in astrocytes were defined. As little as 1 nM LPA induced a rapid increase in the concentration of intracellular free calcium ([Ca2+]i) in astrocytes from neonatal rat brains. This incr...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1997.69031073.x
更新日期：1997-09-01 00:00:00
abstract：:Several derivatives of conantokin-T (con-T), a naturally occurring, gamma-carboxyglutamate (Gla)-containing peptide with NMDA receptor (NMDAR) antagonist properties, were synthesized and evaluated for their ability to displace [(3)H]MK-801 from adult rat forebrain membranes. Analyses of progressive C-terminal truncati...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2001.00281.x
更新日期：2001-05-01 00:00:00
abstract：:Several members of the tetrahydroisoquinoline (TIQ) family of monoamine alkaloids can be formed from dopamine or its oxidized metabolites and may be involved in the pathogenesis of monoaminergic cell death in Parkinson's disease (PD). Using enantiomeric-selective high-performance liquid chromatography with electrochem...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2008.05709.x
更新日期：2008-12-01 00:00:00
abstract：:Expression of the Ca(2+)-dependent phospholipids binding protein annexin A2 (ANX2) in the brain is thought to be largely associated with brain pathological conditions such as tumor, inflammation, and neurodegeneration. The recent findings that ANX2 heterotetramer is involved in learning and neuronal activities necessi...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2006.04311.x
更新日期：2007-03-01 00:00:00
abstract：:Previous evidence has suggested that brain catecholamine levels are important in the regulation of central angiotensin II receptors. In the present study, the effects of norepinephrine and 3,4-dihydroxyphenylethylamine (dopamine) on angiotensin II receptor regulation in neuronal cultures from rat hypothalamus and brai...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1986.tb00729.x
更新日期：1986-10-01 00:00:00
abstract：:Sympathetic denervation of the iris muscle produces increases in both the breakdown of phosphatidylinositol 4,5-bisphosphate (PIP2) and in muscle contraction in response to norepinephrine (NE). To shed more light on the biochemical basis underlying this supersensitivity we investigated: the effects of NE on PIP2 break...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1986.tb12930.x
更新日期：1986-01-01 00:00:00
abstract：:A wealth of evidence supports the view that conformational change of the prion protein, PrPC, into a pathogenic isoform, PrPSc, is the hallmark of sporadic, infectious, and inherited forms of prion disease. Although the central role played by PrPSc in the pathogenesis of prion disease is appreciated, the cellular mech...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2003.01819.x
更新日期：2003-06-01 00:00:00
abstract：:Dietary n-6 polyunsaturated fatty acid (PUFA) deprivation in rodents reduces brain arachidonic acid (20:4n-6) concentration and 20:4n-6-preferring cytosolic phospholipase A(2) (cPLA(2) -IVA) and cyclooxygenase (COX)-2 expression, while increasing brain docosahexaenoic acid (DHA, 22:6n-3) concentration and DHA-selectiv...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2011.07597.x
更新日期：2012-03-01 00:00:00
abstract：:Recent evidence supports the emerging hypothesis that the amyloid-β precursor protein C-terminal fragments (APP-CTFs) and dysregulations in both their qualitative and quantitative productions may actively and directly contribute to the neuronal toxicity in early phases of Alzheimer's disease (AD). These new findings r...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.15143
更新日期：2020-08-05 00:00:00
abstract：:Alzheimer's disease (AD) belongs to one of the most multifactorial, complex and heterogeneous morbidity-leading disorders. Despite the extensive research in the field, AD pathogenesis is still at some extend obscure. Mechanisms linking AD with certain comorbidities, namely diabetes mellitus, obesity and dyslipidemia, ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
doi：10.1111/jnc.14256
更新日期：2018-02-01 00:00:00
abstract：:We applied our in vivo fatty acid method to examine concentrations, incorporation, and turnover rates of docosahexaenoic acid (22:6 n-3) in brains of rats subject to a dietary deficiency of alpha-linolenic acid (18:3 n-3) for three generations. Adult deficient and adequate rats of the F3 generation were infused intrav...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.0752392.x
更新日期：2000-12-01 00:00:00
abstract：:We have previously demonstrated hippocampal hyperglutamatergic signaling occurs prior to plaque accumulation in AβPP/PS1 mice. Here, we evaluate 2-Amino-6-(trifluoromethoxy) benzothiazole (riluzole) as an early intervention strategy for Alzheimer's disease (AD), aimed at restoring glutamate neurotransmission prior to ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.15224
更新日期：2020-10-26 00:00:00
abstract：:The effect of N-methyl-D-aspartate (NMDA) receptor antagonists on cell viability was studied in rat primary cortical cells. NMDA antagonists [MK-801 and 2-amino-5-phosphonovalerate (APV)] induced cell shrinkage, nuclear condensation or fragmentation, and internucleosomal DNA fragmentation. Treatment of cells with MK-8...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1999.0730548.x
更新日期：1999-08-01 00:00:00
abstract：:The presynaptic regulation of amino acid release from nerve terminals was investigated using synaptosomes prepared from the rat spinal cord. The basal releases of endogenous glutamate (Glu), aspartate (Asp), and gamma-amino-butyric acid (GABA) were 34.6, 21.5, and 10.0 pmol/min/mg of protein, respectively. Exposure to...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1993.tb03180.x
更新日期：1993-02-01 00:00:00
abstract：:Urotensin-II (U-II), a peptide with multiple vascular effects, is detected in cholinergic neurons of the rat brainstem and spinal cord. Here, the effects of U-II on [Ca2+]i was examined in dissociated rat spinal cord neurons by fura 2 microfluorimetry. The neurons investigated were choline acetyltransferase-positive a...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2002.01196.x
更新日期：2002-11-01 00:00:00
abstract：:The group I metabotropic glutamate receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG) elicited two phases of synchronized neuronal (epileptiform) discharges in hippocampal slices: an initial phase of short duration discharges followed by a phase of prolonged discharges. We assessed the involvement of transient rec...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2006.04377.x
更新日期：2007-04-01 00:00:00
abstract：:The alpha-synuclein (Snca) gene is expressed at higher levels in alcohol-naïve, inbred alcohol-preferring (iP) rats than in alcohol-non preferring (iNP) rats. Snca modulates dopamine transmission and the dopamineregic system, which play a role in mediating the rewarding properties of alcohol consumption. Thus, underst...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2006.04111.x
更新日期：2006-10-01 00:00:00
abstract：:The development of the specific binding sites for L-[3H]glutamic acid (KD = 370 nM) and for [3H]kainic acid (KD = 39 nM) was studied in the rat cerebellum. Specific binding at both sites remains low during the first week after birth but increases markedly during the second and third weeks after birth, when glutamaterg...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1981.tb00491.x
更新日期：1981-08-01 00:00:00
abstract：:In spite of biochemical and autoradiographic evidence for glucocorticoid binding sites in the spinal cord (SC), events occurring after the preliminary step of hormone binding were not studied. In this investigation, we have examined the transformation (activation) of the cytosolic receptor coupled to [3H]dexamethasone...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1985.tb10525.x
更新日期：1985-12-01 00:00:00
abstract：:This study presents the initial characterization of transgenic mice with mutations in a primary zinc-binding residue (H80), either alone or with a G93A mutation. H80G;G93A superoxide dismutase 1 (SOD1) transgenic mice developed paralysis with motor neuron loss, and ubiquitin inclusion-type rather than mitochondrial va...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2011.07360.x
更新日期：2011-09-01 00:00:00
abstract：:A continuous enzyme-linked fluorometric assay was used for determining the characteristics for glutamate exocytosis from guinea-pig cerebrocortical synaptosomes. Ca2+-dependent release can be induced not only by K+, but also by the Na+ channel activator veratridine and the Ca2+ ionophore ionomycin. K+-induced release ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1987.tb03394.x
更新日期：1987-07-01 00:00:00
abstract：:During CNS injury and diseases, nitric oxide (NO) is released at a high flux rate leading to formation of peroxynitrite (ONOO(*)) and other reactive nitrogenous species, which nitrate tyrosines of proteins to form 3-nitrotyrosine (3NY), leading to cell death. Previously, we have found that motor neurons exposed to low...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2009.05884.x
更新日期：2009-04-01 00:00:00
