Novel structural determinants of single-channel conductance in nicotinic acetylcholine and 5-hydroxytryptamine type-3 receptors.

Abstract:

:Nicotinic ACh (acetylcholine) and 5-HT3 (5-hydroxytryptamine type-3) receptors are cation-selective ion channels of the Cys-loop transmitter-gated ion channel superfamily. Numerous lines of evidence indicate that the channel lining domain of such receptors is formed by the alpha-helical M2 domain (second transmembrane domain) contributed by each of five subunits present within the receptor complex. Specific amino acid residues within the M2 domain have accordingly been demonstrated to influence both single-channel conductance (gamma) and ion selectivity. However, it is now clear from work performed on the homomeric 5-HT3A receptor, heteromeric 5-HT3A/5-HT3B receptor and 5-HT3A/5-HT3B receptor subunit chimaeric constructs that an additional major determinant of gamma resides within a cytoplasmic domain of the receptor termed the MA-stretch (membrane-associated stretch). The MA-stretch, within the M3-M4 loop, is not traditionally thought to be implicated in ion permeation and selection. Here, we describe how such observations extend to a representative neuronal nicotinic ACh receptor composed of alpha4 and beta2 subunits and, by inference, probably other members of the Cys-loop family. In addition, we will attempt to interpret our results within the context of a recently developed atomic scale model of the nicotinic ACh receptor of Torpedo marmorata (marbled electric ray).

journal_name

Biochem Soc Trans

authors

Peters JA,Carland JE,Cooper MA,Livesey MR,Deeb TZ,Hales TG,Lambert JJ

doi

10.1042/BST0340882

subject

Has Abstract

pub_date

2006-11-01 00:00:00

pages

882-6

issue

Pt 5

eissn

0300-5127

issn

1470-8752

pii

BST0340882

journal_volume

34

pub_type

杂志文章
  • Getting through anaphase: splitting the sisters and beyond.

    abstract::Sister-chromatid cohesion, thought to be primarily mediated by the cohesin complex, is essential for chromosome segregation. The forces holding the two sisters resist the tendency of microtubules to prematurely pull sister DNAs apart and thereby prevent random segregation of the genome during mitosis, and consequent a...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0381639

    authors: Oliveira RA,Nasmyth K

    更新日期:2010-12-01 00:00:00

  • Tetraspanin CD9 in cell migration.

    abstract::Tetraspanin CD9 is associated with integrin adhesion receptors and it was reported that CD9 regulates integrin-dependent cell migration and invasion. Pro- and anti-migratory effects of CD9 have been linked to adhesion-dependent signalling pathways, including phosphorylation of FAK (focal adhesion kinase) and activatio...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0390563

    authors: Powner D,Kopp PM,Monkley SJ,Critchley DR,Berditchevski F

    更新日期:2011-04-01 00:00:00

  • A probabilistic model for the extraction of expression levels from oligonucleotide arrays.

    abstract::In this work we present a probabilistic model to estimate summaries of Affymetrix GeneChip probe level data. Comparisons with two different models were made both on a publicly available dataset and on a study performed in our laboratory, showing that our model performs better for consistency of fold change. ...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/bst0311510

    authors: Milo M,Fazeli A,Niranjan M,Lawrence ND

    更新日期:2003-12-01 00:00:00

  • RNA pseudoknots and the regulation of protein synthesis.

    abstract::RNA pseudoknots are structural elements found in almost all classes of RNA. Pseudoknots form when a single-stranded region in the loop of a hairpin base-pairs with a stretch of complementary nucleotides elsewhere in the RNA chain. This simple folding strategy is capable of generating a large number of stable three-dim...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0360684

    authors: Brierley I,Gilbert RJ,Pennell S

    更新日期:2008-08-01 00:00:00

  • The contribution of neurotrophins to the pathogenesis of allergic asthma.

    abstract::The neurotrophins nerve growth factor, brain-derived neurotrophic factor, NT-3 (neurotrophin 3) and NT-4 are known for regulating neuron development, function and survival. Beyond this, neurotrophins were found to exert multiple effects on non-neuronal cells such as immune cells, smooth muscle and epithelial cells. In...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0340594

    authors: Rochlitzer S,Nassenstein C,Braun A

    更新日期:2006-08-01 00:00:00

  • Inhibition of recombinant GluN1/GluN2A and GluN1/GluN2B N-methyl-D-aspartate receptors by single malt whiskies.

    abstract::NMDARs (N-methyl-D-aspartate receptors) are considered to be a target for the inhibitory actions of ethanol. While profound inhibition of both native and recombinant NMDARs can be observed following the application of high concentrations of ethanol the levels of inhibition seen with lower concentrations of ethanol are...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0371423

    authors: Otton HJ,Janssen A,Wyllie DJ

    更新日期:2009-12-01 00:00:00

  • PI3K-signalling in B- and T-cells: insights from gene-targeted mice.

    abstract::Phosphoinositide 3-kinases (PI3Ks) are important signalling enzymes in most cell types. Recent gene targeting studies have shed light on the importance of this family of lipid kinases in the immune system, and the complex mechanisms by which these kinases are regulated in vivo. We have recently reported a phenotype of...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/bst0310270

    authors: Okkenhaug K,Vanhaesebroeck B

    更新日期:2003-02-01 00:00:00

  • IRES-dependent regulation of FGF-2 mRNA translation in pathophysiological conditions in the mouse.

    abstract::The mRNA coding for FGF-2 (fibroblast growth factor 2), a major angiogenic factor, is translated by an IRES (internal ribosome entry site)-dependent mechanism. We have studied the role of the IRES in the regulation of FGF-2 expression in vivo, under pathophysiological conditions, by creating transgenic mice lines expr...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20060017

    authors: Gonzalez-Herrera IG,Prado-Lourenco L,Teshima-Kondo S,Kondo K,Cabon F,Arnal JF,Bayard F,Prats AC

    更新日期:2006-02-01 00:00:00

  • Multiple glucose 6-phosphate pools or channelling of flux in diverse pathways?

    abstract::Glucose 6-phosphate is an intermediate of pathways of glucose utilization and production as well as a regulator of enzyme activity and gene expression. Studies on the latter functions are in part based on measurement of the glucose 6-phosphate content in a whole-cell extract. Several studies have suggested that there ...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/

    authors: Agius L,Centelles J,Cascante M

    更新日期:2002-04-01 00:00:00

  • Coagulation cascade proteases and tissue fibrosis.

    abstract::Fibrotic disorders of the liver, kidney and lung are associated with excessive deposition of extracellular matrix proteins and ongoing coagulation-cascade activity. In addition to their critical roles in blood coagulation, thrombin and the immediate upstream coagulation proteases, Factors Xa and VIIa, influence numero...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/

    authors: Chambers RC,Laurent GJ

    更新日期:2002-04-01 00:00:00

  • Role of the phosphoinositide pathway in the light-dependent C4 phosphoenolpyruvate carboxylase phosphorylation cascade in Digitaria sanguinalis protoplasts.

    abstract::Stimulus-response coupling in animal cells frequently involves the hydrolysis of PtdIns(4,5)P(2) which is catalysed by phosphoinositide-specific phospholipase C (PI-PLC). There is an increasing body of evidence for PI-PLC-based signalling in plant cells; however, the physiological role of this system remains poorly do...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:

    authors: Coursol S,Pierre JN,Vidal J

    更新日期:2000-12-01 00:00:00

  • Crop reproductive meristems in the genomic era: a brief overview.

    abstract::Modulation of traits beneficial for cultivation and yield is one of the main goals of crop improvement. One of the targets for enhancing productivity is changing the architecture of inflorescences since in many species it determines fruit and seed yield. Inflorescence shape and organization is genetically established ...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST20190441

    authors: Caselli F,Zanarello F,Kater MM,Battaglia R,Gregis V

    更新日期:2020-06-30 00:00:00

  • Probing coupled motions in enzymatic hydrogen tunnelling reactions.

    abstract::Much work has gone into understanding the physical basis of the enormous catalytic power of enzymes over the last 50 years or so. Nevertheless, the detailed mechanism used by Nature's catalysts to speed chemical transformations remains elusive. DHFR (dihydrofolate reductase) has served as a paradigm to study the relat...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0370349

    authors: Allemann RK,Evans RM,Loveridge EJ

    更新日期:2009-04-01 00:00:00

  • Lymphocyte cell motility: the twisting, turning tale of phosphoinositide 3-kinase.

    abstract::The PI3K (phosphoinositide 3-kinase) family of lipid kinases regulate cell motility in diverse organisms and cell types. In mammals, the main PI3K enzyme activated by chemokine receptor signalling is the class IB isoform, p110gamma. Studies of p110gamma-knockout mice have shown an essential function for this isoform i...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0351109

    authors: Oak JS,Matheu MP,Parker I,Cahalan MD,Fruman DA

    更新日期:2007-11-01 00:00:00

  • Mechanistic diversity and regulation of Type II fatty acid synthesis.

    abstract::Fatty acid biosynthesis is catalysed in most bacteria by a group of highly conserved proteins known as the Type II fatty acid synthase (FAS) system. The Type II system organization is distinct from its mammalian counterpart and offers several unique sites for selective inhibition by antibacterial agents. There has bee...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/bst0301050

    authors: Marrakchi H,Zhang YM,Rock CO

    更新日期:2002-11-01 00:00:00

  • Definitive endoderm: a key step in coaxing human embryonic stem cells into transplantable beta-cells.

    abstract::Using the Edmonton protocol, a number of patients with Type 1 diabetes mellitus have remained insulin-independent for prolonged periods of time. In spite of this success, transplantation of islets from cadaver donors will remain a therapy for very few patients owing to a lack of donors. Thus, if cell therapy should be...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0360272

    authors: Semb H

    更新日期:2008-06-01 00:00:00

  • Anticipating mechanisms of resistance to PI3K inhibition in breast cancer: a challenge in the era of precision medicine.

    abstract::Frequent subversion of the PI3K (phosphoinositide 3-kinase) pathway during neoplastic transformation contributes to several hallmarks of cancer that result in a competitive advantage for cancer cells. Deregulation of this pathway can be the result of genomic alterations such as PIK3CA mutation, PTEN (phosphatase and t...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20140034

    authors: Leroy C,Amante RJ,Bentires-Alj M

    更新日期:2014-08-01 00:00:00

  • Virtual screening: a real screening complement to high-throughput screening.

    abstract::Virtual screening is being routinely used as an integral part of today's hit-identification strategies for, on one hand, prioritizing large corporate screening collections and, on the other hand, to extend the scope of screening to external databases. A brief description of the essential elements required for virtual ...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/bst0300797

    authors: Mestres J

    更新日期:2002-08-01 00:00:00

  • Interactions between Epac1 and ezrin in the control of endothelial barrier function.

    abstract::Loss of barrier function in the vasculature promotes inflammatory signalling which in turn contributes to the progression of cardiovascular disease. cAMP can protect against endothelial dysfunction through the effectors PKA (protein kinase A) and Epac (exchange protein directly activated by cAMP). The present review o...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20130271

    authors: Parnell E,Yarwood SJ

    更新日期:2014-04-01 00:00:00

  • Protein kinase C in cellular transformation: a valid target for therapy?

    abstract::The protein kinase C (PKC) family of serine/threonine protein kinases share structural homology, while exhibiting substantial functional diversity. PKC isoforms are ubiquitously expressed in tissues which makes it difficult to define roles for individual isoforms, with complexity compounded by the finding that PKC iso...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20140255

    authors: Tarafdar A,Michie AM

    更新日期:2014-12-01 00:00:00

  • Colicin M, a peptidoglycan lipid-II-degrading enzyme: potential use for antibacterial means?

    abstract::Colicins are proteins produced by some strains of Escherichia coli to kill competitors belonging to the same species. Among them, ColM (colicin M) is the only one that blocks the biosynthesis of peptidoglycan, a specific bacterial cell-wall polymer essential for cell integrity. ColM acts in the periplasm by hydrolysin...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST20120189

    authors: Touzé T,Barreteau H,El Ghachi M,Bouhss A,Barnéoud-Arnoulet A,Patin D,Sacco E,Blanot D,Arthur M,Duché D,Lloubès R,Mengin-Lecreulx D

    更新日期:2012-12-01 00:00:00

  • A novel function of lipid droplets in regulating longevity.

    abstract::Growing evidence supports the view that LDs (lipid droplets) are dynamic organelles that can serve both as an intracellular signalling compartment and as an organizing platform orchestrating many vital processes in eukaryotic cells. It has become clear that the LDs-confined deposition and lipolytic degradation of neut...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0371050

    authors: Goldberg AA,Bourque SD,Kyryakov P,Boukh-Viner T,Gregg C,Beach A,Burstein MT,Machkalyan G,Richard V,Rampersad S,Titorenko VI

    更新日期:2009-10-01 00:00:00

  • Amino-acid-induced signalling via the SPS-sensing pathway in yeast.

    abstract::Yeast cells rely on the SPS-sensing pathway to respond to extracellular amino acids. This nutrient-induced signal transduction pathway regulates gene expression by controlling the activity of two redundant transcription factors: Stp1 and Stp2. These factors are synthesized as latent cytoplasmic proteins with N-termina...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0370242

    authors: Ljungdahl PO

    更新日期:2009-02-01 00:00:00

  • Regional differences in protein production by human adipose tissue.

    abstract::Human adipose tissue has an important protein secretory function. Cytokines, hormones, prohormones and enzymes are secreted from fat cells and act in an endocrine or paracrine fashion. The production of several of these proteins is affected by obesity; normally there is an increase in the obese state. Protein producti...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/bst0290072

    authors: Arner P

    更新日期:2001-05-01 00:00:00

  • Recycling domains in plant cell morphogenesis: small GTPase effectors, plasma membrane signalling and the exocyst.

    abstract::The Rho/Rop small GTPase regulatory module is central for initiating exocytotically ACDs (active cortical domains) in plant cell cortex, and a growing array of Rop regulators and effectors are being discovered in plants. Structural membrane phospholipids are important constituents of cells as well as signals, and phos...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0380723

    authors: Zárský V,Potocký M

    更新日期:2010-04-01 00:00:00

  • The use of in situ haemoglobin-free perfused liver in metabolic-control analysis.

    abstract::In this study the network of ATP-consuming and -producing reactions, interacting via the cytosolic ATP/ADP+P(i) system, was studied for the first time in an intact organ, the isolated perfused rat liver, using top-down metabolic-control analysis. Flux control in the metabolically resting state (only oxidative phosphor...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/bst0280109

    authors: Soboll S,Brown GC

    更新日期:2000-02-01 00:00:00

  • Neuropilin regulation of angiogenesis.

    abstract::Blood vessel formation during vertebrate development relies on a process called angiogenesis and is essential for organ growth and tissue viability. In addition, angiogenesis leads to pathological blood vessel growth in diseases with tissue ischaemia, such as neovascular eye disease and cancer. Neuropilin 1 (NRP1) is ...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20140244

    authors: Lampropoulou A,Ruhrberg C

    更新日期:2014-12-01 00:00:00

  • Structural elements involved in activation of the gamma-aminobutyric acid type A (GABAA) receptor.

    abstract::Ligand-gated ion channels function as rapid signal transducers, converting chemical signals (in the form of neurotransmitters) into electrical signals in the postsynaptic neuron. This is achieved by the recognition of neurotransmitter at its specific-binding sites, which then triggers the opening of an ion channel ('g...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0320540

    authors: Kash TL,Trudell JR,Harrison NL

    更新日期:2004-06-01 00:00:00

  • An integrated transcriptional switch at the β-selection checkpoint determines T cell survival, development and leukaemogenesis.

    abstract::In T cell development, a pivotal decision-making stage, termed β-selection, integrates a TCRβ checkpoint to coordinate survival, proliferation and differentiation to an αβ T cell. Here, we review how transcriptional regulation coordinates fate determination in early T cell development to enable β-selection. Errors in ...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20180414

    authors: Chann AS,Russell SM

    更新日期:2019-08-30 00:00:00

  • The assimilatory nitrate reduction system of the phototrophic bacterium Rhodobacter capsulatus E1F1.

    abstract::The phototrophic bacterium Rhodobacter capsulatus E1F1 assimilates nitrate under anaerobic phototrophic growth conditions. A 17 kb DNA region encoding the nitrate assimilation (nas) system of this bacterium has been cloned and sequenced. This region includes the genes coding for a putative ABC (ATP-binding cassette)-t...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0340127

    authors: Pino C,Olmo-Mira F,Cabello P,Martínez-Luque M,Castillo F,Roldán MD,Moreno-Vivián C

    更新日期:2006-02-01 00:00:00