Conserved extracellular cysteine pair in the M3 muscarinic acetylcholine receptor is essential for proper receptor cell surface localization but not for G protein coupling.

Abstract:

:Most G protein-coupled receptors contain a conserved pair of extracellular cysteine residues that are predicted to form a disulfide bond linking the first and second extracellular loops. Previous studies have shown that this disulfide bond may be critical for ligand binding, receptor activation, and/or proper receptor folding. However, the potential importance of the two conserved cysteine residues for proper receptor cell surface localization has not been investigated systematically. To address this issue, we used the rat M3 muscarinic receptor as a model system. Most studies were carried out with a modified version of this receptor subtype (lacking potential N-glycosylation sites and the central portion of the third intracellular loop) that could be readily detected via western blot analysis. Cys-->Ala mutant receptors were generated, transiently expressed in COS-7 cells, and then examined for their subcellular distribution and functional properties. ELISA and immunofluorescence studies showed that the presence of both conserved cysteine residues (corresponding to C140 and C220 in the rat M3 muscarinic receptor sequence) is required for efficient expression of the M3 muscarinic receptor on the cell surface. On the other hand, these residues were found not to be essential for protein stability (determined via immunoblotting) and receptor-mediated G protein activation (studied in second messenger assays). These results shed new light on the functional role of the two extracellular cysteine residues present in most G protein-coupled receptors.

journal_name

J Neurochem

authors

Zeng FY,Soldner A,Schöneberg T,Wess J

doi

10.1046/j.1471-4159.1999.0722404.x

keywords:

subject

Has Abstract

pub_date

1999-06-01 00:00:00

pages

2404-14

issue

6

eissn

0022-3042

issn

1471-4159

journal_volume

72

pub_type

杂志文章
  • Chronic electroconvulsive seizures down-regulate expression of the immediate-early genes c-fos and c-jun in rat cerebral cortex.

    abstract::Acute seizures and other stimuli that increase neuronal activity cause a rapid induction of the immediate-early genes c-fos and c-jun, also referred to as nuclear proto-oncogenes, in the nervous system. In the present study, rats were administered one or more electroconvulsive seizures (ECS) and the responsiveness of ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1990.tb04892.x

    authors: Winston SM,Hayward MD,Nestler EJ,Duman RS

    更新日期:1990-06-01 00:00:00

  • Relative contribution of different receptor subtypes in the response of neuroblastoma cells to tumor necrosis factor-alpha.

    abstract::The effect of tumor necrosis factor-alpha (TNF-alpha) on neuronal viability has been investigated in the SK-N-BE neuroblastoma cell line. These cells undergo differentiation upon chronic treatment with retinoic acid. Exposure of SK-N-BE cells to TNF-alpha produced a proliferative response in undifferentiated cells, wh...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2000.0751172.x

    authors: Condorelli F,Sortino MA,Stella AM,Canonico PL

    更新日期:2000-09-01 00:00:00

  • Protective effects of extracellular acidosis and blockade of sodium/hydrogen ion exchange during recovery from metabolic inhibition in neuronal tissue culture.

    abstract::Acidosis is a universal response of tissue to ischemia. In the brain, severe acidosis has been linked to worsening of cerebral infarction. However, milder acidosis can have protective effects. As part of our investigations of the therapeutic window in our neuronal tissue culture model of ischemia, we investigated the ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1996.67062379.x

    authors: Vornov JJ,Thomas AG,Jo D

    更新日期:1996-12-01 00:00:00

  • Effect of changing potassium ion concentrations on rat cerebral slices in vitro: a study during development.

    abstract::Adult rat cerebral cortex slices when incubated in media in increasing K+ concentrations, from 3 to 20 mM ("physiological" conditions), exhibited an increase of Ki+ and a decrease of Nai+ and Cli-. This phenomenon appeared at 30 days postnatally, which is fairly late during development. Over 20 mM-K+ ("pathological" c...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1981.tb00440.x

    authors: Grisar T,Franck G

    更新日期:1981-05-01 00:00:00

  • Novel therapeutic strategies targeting innate immune responses and early inflammation after stroke.

    abstract::Post-ischemic inflammation is an essential step in the progression of ischemic stroke. This review focuses on the function of infiltrating immune cells, macrophages, and T cells, in ischemic brain injury. The brain is a sterile organ; however, the activation of Toll-like receptor (TLR) 2 and TLR4 is pivotal in the beg...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章,评审

    doi:10.1111/j.1471-4159.2012.07941.x

    authors: Shichita T,Ago T,Kamouchi M,Kitazono T,Yoshimura A,Ooboshi H

    更新日期:2012-11-01 00:00:00

  • Steroid hormones block amyloid fibril-induced 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) formazan exocytosis: relationship to neurotoxicity.

    abstract::Perhaps the most reproducible early event induced by the interaction of amyloid beta peptide (A beta) with the cell is the inhibition of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. We recently demonstrated that cytotoxic amyloid peptides such as A beta and human amylin inhibi...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1998.71062322.x

    authors: Liu Y,Schubert D

    更新日期:1998-12-01 00:00:00

  • Extracellular release of newly synthesized sphingosine-1-phosphate by cerebellar granule cells and astrocytes.

    abstract::Sphingosine-1-phosphate (S1P) is a potent biomediator that can act as either an intracellular or an intercellular messenger. In the nervous system it exerts a wide range of actions, and specific membrane receptors for it have been identified in various regions. However, the physiological origin of extracellular S1P in...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2004.02955.x

    authors: Anelli V,Bassi R,Tettamanti G,Viani P,Riboni L

    更新日期:2005-03-01 00:00:00

  • Functional reconstitution of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors from rat brain.

    abstract::Glutamate receptors belonging to the subclass specifically activated by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) were solubilized from rat forebrain membranes with Triton X-100 and partially purified through a series of three chromatographic steps. Specific [3H]AMPA binding increased 30-60-fold ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1992.tb11038.x

    authors: Bahr BA,Vodyanoy V,Hall RA,Suppiramaniam V,Kessler M,Sumikawa K,Lynch G

    更新日期:1992-11-01 00:00:00

  • GT3 synthesis in the proximal Golgi occurs in a compartment different from those for GD3 and GM3 synthesis.

    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

    authors: Rosales Fritz VM,Maxzúd MK,Maccioni HJ

    更新日期:1996-10-01 00:00:00

  • Distribution of calcitonin gene-related peptide in rat and rabbit spinal cords: effect of intrathecal 5,7-dihydroxytryptamine.

    abstract::Calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) was measured in selected regions of the cervical, thoracic, and lumbar spinal cord of untreated rabbits and, following intrathecal injection of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), in the thoracolumbar cord in rats using a sheep ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1992.tb08434.x

    authors: Fone KC

    更新日期:1992-10-01 00:00:00

  • Time course changes in the dopaminergic nigrostriatal system following transection of the medial forebrain bundle: detection of oxidatively modified proteins in substantia nigra.

    abstract::We studied the time course of oxidatively modified proteins in the nigrostriatal dopaminergic system following transection of the medial forebrain bundle by quantifying the number of carbonyl groups coupled to striatal and nigral protein homogenates, an index of metal-catalyzed oxidations. We found a striking effect o...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1997.68062458.x

    authors: Venero JL,Revuelta M,Cano J,Machado A

    更新日期:1997-06-01 00:00:00

  • Amyloid beta proteins inhibit Cl(-)-ATPase activity in cultured rat hippocampal neurons.

    abstract::Cl(-)-ATPase in the CNS is a candidate for an outwardly directed neuronal Cl(-) transporter requiring phosphatidylinositol-4-phosphate (PI4P) for its optimal activity. To test its pathophysiological changes in a phosphatidylinositol (PI) metabolism disorder, the effects of neurotoxic factors in Alzheimer's disease (AD...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2001.00446.x

    authors: Yagyu K,Kitagawa K,Irie T,Wu B,Zeng XT,Hattori N,Inagaki C

    更新日期:2001-08-01 00:00:00

  • The structural specificity of choline transport into cholinergic nerve terminals.

    abstract::The accumulation of choline, homocholine, and 4-hydroxybutyltrimethylammonium by rat brain synaptosomes was measured; the choline uptake mechanism transported homocholine but not hydroxybutyltrimethylammonium, which, in addition, did not block choline accumulation. In cats' superior cervical ganglia, preganglionic ner...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1981.tb01732.x

    authors: Collier B

    更新日期:1981-03-01 00:00:00

  • Distribution of preproatrial natriuretic peptide mRNA in rat brain detected by in situ hybridization of DNA oligonucleotides: enrichment in hypothalamic and limbic regions.

    abstract::The expression and distribution of mRNA encoding preproatrial natriuretic peptide (ppANP) in rat brain has been investigated by in situ hybridization of two 35S-labeled synthetic DNA oligonucleotides, based on a cDNA clone sequence that encodes rat ppANP. The highest relative concentrations of ppANP mRNA were detected...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1992.tb09434.x

    authors: Gundlach AL,Knobe KE

    更新日期:1992-08-01 00:00:00

  • Characterization of Dp71Δ(78-79), a novel dystrophin mutant that stimulates PC12 cell differentiation.

    abstract::Dp71 has an important role in the central nervous system. To better understand the function of Dp71 domains in neuronal differentiation, PC12 cells were stably transfected with a dystrophin mutant, Dp71Δ(78-79) , which lacks exons 78 and 79. Based on the percentage of cells bearing neurites and neurite length analyses...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2011.07347.x

    authors: Aragón J,Romo-Yáñez J,Martínez-Herrera A,Ceja V,Rendon A,Montañez C

    更新日期:2011-11-01 00:00:00

  • Phospholipid methylation and noradrenaline exchanges in a synaptosomal preparation from the rat brain.

    abstract::When synaptosomes from rat brain were incubated with S-adenosylmethionine (10(-3) M), noradrenaline uptake and KCl-stimulated release were decreased. These effects were dependent on MgCl2, temperature, and incubation time. We have investigated the enzymatic methylation of phosphatidylethanolamine to give phosphatidylc...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1982.tb06641.x

    authors: Fonlupt P,Rey C,Pacheco H

    更新日期:1982-06-01 00:00:00

  • Amyloid precursor protein knockdown by siRNA impairs spontaneous alternation in adult mice.

    abstract::The cleavage-product of amyloid precursor protein (APP) constitutes the core component of plaques found in the brains of Alzheimer's disease (AD) patients. APP is ubiquitously expressed and its precise physiological functions remain unclear. This protein has been proposed to regulate synaptic function and processes un...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2007.04672.x

    authors: Senechal Y,Kelly PH,Cryan JF,Natt F,Dev KK

    更新日期:2007-09-01 00:00:00

  • Methamphetamine-induced depression of monoamine synthesis in the rat: development of tolerance.

    abstract::Animals treated with high doses of amphetamines have been used as a model of schizophrenia due to the similarities between the psychosis associated with this mental disorder and that induced by chronic amphetamine abuse. When administered to naive rats in high doses, the amphetamine-like CNS stimulant methamphetamine ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1985.tb12893.x

    authors: Schmidt CJ,Sonsalla PK,Hanson GR,Peat MA,Gibb JW

    更新日期:1985-03-01 00:00:00

  • Stereoselective nicotine-induced release of dopamine from striatal synaptosomes: concentration dependence and repetitive stimulation.

    abstract::Using a sensitive perfusion system we have studied the nicotine-induced release of [3H]dopamine ([( 3H]DA) from striatal synaptosomes. Nicotine-evoked release was concentration dependent with an EC50 of 3.8 microM. The response to 1 microM nicotine was comparable to that to 16 mM K+; 10 microM veratridine evoked a lar...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1988.tb10582.x

    authors: Rapier C,Lunt GG,Wonnacott S

    更新日期:1988-04-01 00:00:00

  • Zebrafish as a new animal model for movement disorders.

    abstract::The zebrafish, long recognized as a model organism for the analysis of basic developmental processes, is now also emerging as an alternative animal model for human diseases. This review will first provide an overview of the particular characteristics of zebrafish in general and their dopaminergic nervous system in par...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章,评审

    doi:10.1111/j.1471-4159.2008.05463.x

    authors: Flinn L,Bretaud S,Lo C,Ingham PW,Bandmann O

    更新日期:2008-09-01 00:00:00

  • Down-regulation of Bcl-2 and Bcl-xL expression with bispecific antisense treatment in glioblastoma cell lines induce cell death.

    abstract::The functions of the antiapoptotic proteins Bcl-2 and Bcl-xL were examined in glioblastoma cells. Expression of both Bcl-2 and Bcl-xL were found to be elevated in protein lysates from seven early passage cell lines derived from human glioblastoma tumors compared with non-neoplastic glial cells. Down-regulation of both...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2003.01522.x

    authors: Jiang Z,Zheng X,Rich KM

    更新日期:2003-01-01 00:00:00

  • Differential ultrastructural localization of myelin basic protein, myelin/oligodendroglial glycoprotein, and 2',3'-cyclic nucleotide 3'-phosphodiesterase in the CNS of adult rats.

    abstract::In a light and electron microscopic immunocytochemical study we have examined the distribution of myelin basic protein (MBP), 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP), and myelin/oligodendroglial glycoprotein (MOG) within CNS myelin sheaths and oligodendrocytes of adult Sprague-Dawley rats. Ultrastructural i...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1989.tb10930.x

    authors: Brunner C,Lassmann H,Waehneldt TV,Matthieu JM,Linington C

    更新日期:1989-01-01 00:00:00

  • The significance of mast cells as a source of histamine in the mouse brain.

    abstract::Knowledge of the relative contributions of mast cells and neurons to the overall pool of histamine in the brain is a prerequisite to determining the significance and role of this amine in brain function. Consequently, we analyzed the levels of brain histamine in four genotypes (+/+, W/+, Wv/+, and W/Wv) of WBB6F1 mice...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1984.tb02743.x

    authors: Orr EL,Pace KR

    更新日期:1984-03-01 00:00:00

  • GM3 alpha2,8-sialyltransferase (GD3 synthase): protein characterization and sub-golgi location in CHO-K1 cells.

    abstract::GD3 synthase (Sial-T2) is a key enzyme of ganglioside synthesis that, in concert with GM2 synthase (GalNAc-T), regulates the ratio of a- and b-pathway gangliosides. In this work, we study the sub-Golgi location of an epitope-tagged version of chicken Sial-T2 transfected to CHO-K1 cells. The expressed protein was enzym...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2000.0741711.x

    authors: Daniotti JL,Martina JA,Giraudo CG,Zurita AR,Maccioni HJ

    更新日期:2000-04-01 00:00:00

  • In vitro release of endogenous dopamine from the striatum of the weaver mutant mouse.

    abstract::The weaver mutant mouse has a genetically determined defect in the nigrostriatal dopaminergic system. The present study was undertaken to test the hypothesis that in the weaver mutant mouse, striatal nerve terminals undergo compensatory changes in response to this deficiency. To test this hypothesis, we studied the ba...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1991.tb06341.x

    authors: Simon JR,Yu H,Richter JA,Vasko MR,Ghetti B

    更新日期:1991-11-01 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

  • Increased inositol 1,4,5-trisphosphate accumulation correlates with an up-regulation of bradykinin receptors in Alzheimer's disease.

    abstract::An alteration in signal transduction systems in Alzheimer's disease (AD) would likely be of pathophysiological significance, because these processes control normal brain functions. Previously, a diminished beta-adrenergic-mediated cyclic AMP response was found in cultured fibroblasts from AD patients. Because cross-ta...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1995.64020761.x

    authors: Huang HM,Lin TA,Sun GY,Gibson GE

    更新日期:1995-02-01 00:00:00

  • Complement C3 and C4 expression in C1q sufficient and deficient mouse models of Alzheimer's disease.

    abstract::Alzheimer's disease (AD) is a neurodegenerative disease resulting in progressive cognitive decline. Amyloid plaque deposits consisting specifically of beta-amyloid peptides that have formed fibrils displaying beta-pleated sheet conformation are associated with activated microglia and astrocytes, are colocalized with C...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2008.05558.x

    authors: Zhou J,Fonseca MI,Pisalyaput K,Tenner AJ

    更新日期:2008-09-01 00:00:00

  • Clearing amyloid through the blood-brain barrier.

    abstract::According to the amyloid hypothesis, accumulation of amyloid beta-peptide (A beta) in the brain is the primary pathogenic event in Alzheimer's disease (AD). Recent evidence indicates that A beta within the intravascular space is linked to A beta deposited in the brain suggesting that transport of A beta between the br...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章,评审

    doi:10.1111/j.1471-4159.2004.02385.x

    authors: Zlokovic BV

    更新日期:2004-05-01 00:00:00

  • Escalation of cocaine self-administration does not depend on altered cocaine-induced nucleus accumbens dopamine levels.

    abstract::Previous studies showed that prolonged access to cocaine or heroin self-administration (long access, or LgA) produces an escalation in drug intake not observed with limited access to the drug (short access, or ShA). The present experiment employed in vivo microdialysis to test the role of alterations in drug pharmacok...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2003.01833.x

    authors: Ahmed SH,Lin D,Koob GF,Parsons LH

    更新日期:2003-07-01 00:00:00