The roles of aromatic residues in the glycine receptor transmembrane domain.

Abstract:

BACKGROUND:Cys-loop receptors play important roles in fast neuronal signal transmission. Functional receptors are pentamers, with each subunit having an extracellular, transmembrane (TM) and intracellular domain. Each TM domain contains 4 α-helices (M1-M4) joined by loops of varying lengths. Many of the amino acid residues that constitute these α-helices are hydrophobic, and there has been particular interest in aromatic residues, especially those in M4, which have the potential to contribute to the assembly and function of the receptor via a range of interactions with nearby residues. RESULTS:Here we show that many aromatic residues in the M1, M3 and M4 α-helices of the glycine receptor are involved in the function of the receptor. The residues were explored by creating a range of mutant receptors, characterising them using two electrode voltage clamp in Xenopus oocytes, and interpreting changes in receptor parameters using currently available structural information on the open and closed states of the receptor. For 7 residues function was ablated with an Ala substitution: 3 Tyr residues at the extracellular end of M1, 2 Trp residues located towards the centers of M1 and M3, and a Phe and a Tyr residue in M4. For many of these an alternative aromatic residue restored wild-type-like function indicating the importance of the π ring. EC50s were increased with Ala substitution of 8 other aromatic residues, with those in M1 and M4 also having reduced currents, indicating a role in receptor assembly. The structure shows many potential interactions with nearby residues, especially between those that form the M1/M3/M4 interface, and we identify those that are supported by the functional data. CONCLUSION:The data reveal the importance and interactions of aromatic residues in the GlyR M1, M3 and M4 α-helices, many of which are essential for receptor function.

journal_name

BMC Neurosci

journal_title

BMC neuroscience

authors

Tang B,Lummis SCR

doi

10.1186/s12868-018-0454-8

subject

Has Abstract

pub_date

2018-09-06 00:00:00

pages

53

issue

1

issn

1471-2202

pii

10.1186/s12868-018-0454-8

journal_volume

19

pub_type

杂志文章
  • The BOLD response and the gamma oscillations respond differently than evoked potentials: an interleaved EEG-fMRI study.

    abstract:BACKGROUND:The integration of EEG and fMRI is attractive because of their complementary precision regarding time and space. But the relationship between the indirect hemodynamic fMRI signal and the more direct EEG signal is uncertain. Event-related EEG responses can be analyzed in two different ways, reflecting two dif...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/1471-2202-4-22

    authors: Foucher JR,Otzenberger H,Gounot D

    更新日期:2003-09-19 00:00:00

  • A few strong connections: optimizing information retention in neuronal avalanches.

    abstract:BACKGROUND:How living neural networks retain information is still incompletely understood. Two prominent ideas on this topic have developed in parallel, but have remained somewhat unconnected. The first of these, the "synaptic hypothesis," holds that information can be retained in synaptic connection strengths, or weig...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/1471-2202-11-3

    authors: Chen W,Hobbs JP,Tang A,Beggs JM

    更新日期:2010-01-06 00:00:00

  • Death Associated Protein Kinase (DAPK) -mediated neurodegenerative mechanisms in nematode excitotoxicity.

    abstract:BACKGROUND:Excitotoxicity (the toxic overstimulation of neurons by the excitatory transmitter Glutamate) is a central process in widespread neurodegenerative conditions such as brain ischemia and chronic neurological diseases. Many mechanisms have been suggested to mediate excitotoxicity, but their significance across ...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/s12868-015-0158-2

    authors: Del Rosario JS,Feldmann KG,Ahmed T,Amjad U,Ko B,An J,Mahmud T,Salama M,Mei S,Asemota D,Mano I

    更新日期:2015-04-23 00:00:00

  • Cholecystokinin receptor-1 mediates the inhibitory effects of exogenous cholecystokinin octapeptide on cellular morphine dependence.

    abstract:BACKGROUND:Cholecystokinin octapeptide (CCK-8), the most potent endogenous anti-opioid peptide, has been shown to regulate the processes of morphine dependence. In our previous study, we found that exogenous CCK-8 attenuated naloxone induced withdrawal symptoms. To investigate the precise effect of exogenous CCK-8 and ...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/1471-2202-13-63

    authors: Wen D,Ma CL,Zhang YJ,Meng YX,Ni ZY,Li SJ,Cong B

    更新日期:2012-06-08 00:00:00

  • Peripheral injection of human umbilical cord blood stimulates neurogenesis in the aged rat brain.

    abstract:BACKGROUND:Neurogenesis continues to occur throughout life but dramatically decreases with increasing age. This decrease is mostly related to a decline in proliferative activity as a result of an impoverishment of the microenvironment of the aged brain, including a reduction in trophic factors and increased inflammatio...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/1471-2202-9-22

    authors: Bachstetter AD,Pabon MM,Cole MJ,Hudson CE,Sanberg PR,Willing AE,Bickford PC,Gemma C

    更新日期:2008-02-14 00:00:00

  • Sensitive detection of Aβ protofibrils by proximity ligation--relevance for Alzheimer's disease.

    abstract:BACKGROUND:Protein aggregation plays important roles in several neurodegenerative disorders. For instance, insoluble aggregates of phosphorylated tau and of Aβ peptides are cornerstones in the pathology of Alzheimer's disease. Soluble protein aggregates are therefore potential diagnostic and prognostic biomarkers for t...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/1471-2202-11-124

    authors: Kamali-Moghaddam M,Pettersson FE,Wu D,Englund H,Darmanis S,Lord A,Tavoosidana G,Sehlin D,Gustafsdottir S,Nilsson LN,Lannfelt L,Landegren U

    更新日期:2010-10-05 00:00:00

  • Long-lasting anxiolytic effect of neural precursor cells freshly prepared but not neurosphere-derived cell transplantation in newborn rats.

    abstract:BACKGROUND:The GABAergic system plays an important role in modulating levels of anxiety. When transplanted into the brain, precursor cells from the medial ganglionic eminence (MGE) have the ability to differentiate into GABAergic interneurons and modify the inhibitory tone in the host brain. Currently, two methods have...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/1471-2202-15-94

    authors: Romariz SA,Paiva Dde S,Valente MF,Barnabé GF,Frussa-Filho R,Barbosa-Silva RC,Calcagnotto ME,Longo BM

    更新日期:2014-08-02 00:00:00

  • Noise alters guinea pig's blood-labyrinth barrier ultrastructure and permeability along with a decrease of cochlear Claudin-5 and Occludin.

    abstract:BACKGROUND:Noise exposure (NE) is a severe modern health hazard that induces hearing impairment. However, the noise-induced ultrastructural changes of blood-labyrinth barrier (BLB) and the potential involvements of tight junction proteins (TJP) remain inconclusive. We investigated the effects of NE on not only the ultr...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/s12868-014-0136-0

    authors: Wu YX,Zhu GX,Liu XQ,Sun F,Zhou K,Wang S,Wang CM,Jia JW,Song JT,Lu LJ

    更新日期:2014-12-24 00:00:00

  • Imprinting modulates processing of visual information in the visual wulst of chicks.

    abstract:BACKGROUND:Imprinting behavior is one form of learning and memory in precocial birds. With the aim of elucidating of the neural basis for visual imprinting, we focused on visual information processing. RESULTS:A lesion in the visual wulst, which is similar functionally to the mammalian visual cortex, caused anterograd...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/1471-2202-7-75

    authors: Maekawa F,Komine O,Sato K,Kanamatsu T,Uchimura M,Tanaka K,Ohki-Hamazaki H

    更新日期:2006-11-14 00:00:00

  • NKCC1 downregulation induces hyperpolarizing shift of GABA responsiveness at near term fetal stages in rat cultured dorsal root ganglion neurons.

    abstract:BACKGROUND:GABAA receptor-mediated neurotransmission is greatly influenced by cation-chloride cotransporter activity during developmental stages. In embryonic neurons Na-K-2Cl (NKCC1) cotransporters mediate active chloride uptake, thus increasing the intracellular chloride concentration associated with GABA-induced dep...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/s12868-015-0180-4

    authors: Chabwine JN,Talavera K,Van Den Bosch L,Callewaert G

    更新日期:2015-07-14 00:00:00

  • Culture but not gender modulates amygdala activation during explicit emotion recognition.

    abstract:BACKGROUND:Mounting evidence indicates that humans have significant difficulties in understanding emotional expressions from individuals of different ethnic backgrounds, leading to reduced recognition accuracy and stronger amygdala activation. However, the impact of gender on the behavioral and neural reactions during ...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/1471-2202-13-54

    authors: Derntl B,Habel U,Robinson S,Windischberger C,Kryspin-Exner I,Gur RC,Moser E

    更新日期:2012-05-29 00:00:00

  • Agmatine protects retinal ganglion cells from hypoxia-induced apoptosis in transformed rat retinal ganglion cell line.

    abstract:BACKGROUND:Agmatine is an endogenous polyamine formed by the decarboxylation of L-arginine. We investigated the protective effects of agmatine against hypoxia-induced apoptosis of immortalized rat retinal ganglion cells (RGC-5). RGC-5 cells were cultured in a closed hypoxic chamber (5% O2) with or without agmatine. Cel...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/1471-2202-8-81

    authors: Hong S,Lee JE,Kim CY,Seong GJ

    更新日期:2007-10-02 00:00:00

  • Chronic nicotine pretreatment is sufficient to upregulate α4* nicotinic receptors and increase oral nicotine self-administration in mice.

    abstract:BACKGROUND:Understanding the underlying causes of nicotine addiction will require a multidisciplinary approach examining the key molecular, cellular and neuronal circuit functional changes that drive escalating levels of nicotine self-administration. In this study, we examined whether mice pretreated with chronic nicot...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/1471-2202-15-89

    authors: Renda A,Nashmi R

    更新日期:2014-07-19 00:00:00

  • Separate urinary bladder and prostate neurons in the central nervous system of the rat: simultaneous labeling with two immunohistochemically distinguishable pseudorabies viruses.

    abstract:BACKGROUND:This work examines the central nervous system distribution of virus-labeled neurons from the rat urinary bladder and the prostate simultaneously within the same tissue sections. Two immunohistochemically distinct pseudorabies virus strains were simultaneously injected into male Sprague Dawley rats (approxima...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/1471-2202-3-8

    authors: Nadelhaft I,Miranda-Sousa AJ,Vera PL

    更新日期:2002-07-12 00:00:00

  • Efficacy of antidotes (midazolam, atropine and HI-6) on nerve agent induced molecular and neuropathological changes.

    abstract:BACKGROUND:Recent alleged attacks with nerve agent sarin on civilians in Syria indicate their potential threat to both civilian and military population. Acute nerve agent exposure can cause rapid death or leads to multiple and long term neurological effects. The biochemical changes that occur following nerve agent expo...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/1471-2202-15-47

    authors: RamaRao G,Afley P,Acharya J,Bhattacharya BK

    更新日期:2014-04-04 00:00:00

  • Wheel running from a juvenile age delays onset of specific motor deficits but does not alter protein aggregate density in a mouse model of Huntington's disease.

    abstract:BACKGROUND:Huntington's disease (HD) is a neurodegenerative disorder predominantly affecting the cerebral cortex and striatum. Transgenic mice (R6/1 line), expressing a CAG repeat encoding an expanded polyglutamine tract in the N-terminus of the huntingtin protein, closely model HD. We have previously shown that enviro...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/1471-2202-9-34

    authors: van Dellen A,Cordery PM,Spires TL,Blakemore C,Hannan AJ

    更新日期:2008-04-01 00:00:00

  • Immunization with neural derived peptides plus scar removal induces a permissive microenvironment, and improves locomotor recovery after chronic spinal cord injury.

    abstract:BACKGROUND:Immunization with neural derived peptides (INDP) as well as scar removal-separately-have shown to induce morphological and functional improvement after spinal cord injury (SCI). In the present study, we compared the effect of INDP alone versus INDP with scar removal on motor recovery, regeneration-associated...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/s12868-016-0331-2

    authors: Rodríguez-Barrera R,Flores-Romero A,Fernández-Presas AM,García-Vences E,Silva-García R,Konigsberg M,Blancas-Espinoza L,Buzoianu-Anguiano V,Soria-Zavala K,Suárez-Meade P,Ibarra A

    更新日期:2017-01-05 00:00:00

  • Quantitative genome-wide association analyses of receptive language in the Danish High Risk and Resilience Study.

    abstract:BACKGROUND:One of the most basic human traits is language. Linguistic ability, and disability, have been shown to have a strong genetic component in family and twin studies, but molecular genetic studies of language phenotypes are scarce, relative to studies of other cognitive traits and neurodevelopmental phenotypes. ...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/s12868-020-00581-5

    authors: Nudel R,Christiani CAJ,Ohland J,Uddin MJ,Hemager N,Ellersgaard D,Spang KS,Burton BK,Greve AN,Gantriis DL,Bybjerg-Grauholm J,Jepsen JRM,Thorup AAE,Mors O,Werge T,Nordentoft M

    更新日期:2020-07-07 00:00:00

  • MK801 attenuates secondary injury in a mouse experimental compression model of spinal cord trauma.

    abstract:BACKGROUND:Glutamergic excitotoxicity has been shown to play a deleterious role in the pathophysiology of spinal cord injury (SCI). The aim of this study was to investigate the neuroprotective effect of dizocilpine maleate, MK801 (2 mg/Kg, 30 min and 6 hours after injury) in a mice model of SCI. The spinal cord trauma ...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/1471-2202-12-31

    authors: Esposito E,Paterniti I,Mazzon E,Genovese T,Galuppo M,Meli R,Bramanti P,Cuzzocrea S

    更新日期:2011-04-14 00:00:00

  • Stage effects of negative emotion on spatial and verbal working memory.

    abstract:BACKGROUND:The effects of negative emotion on different processing periods in spatial and verbal working memory (WM) and the possible brain mechanism of the interaction between negative emotion and WM were explored using a high-time resolution event-related potential (ERP) technique and time-locked delayed matching-to-...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/1471-2202-11-60

    authors: Li X,Chan RC,Luo YJ

    更新日期:2010-05-07 00:00:00

  • Functional crosstalk in culture between macrophages and trigeminal sensory neurons of a mouse genetic model of migraine.

    abstract:BACKGROUND:Enhanced activity of trigeminal ganglion neurons is thought to underlie neuronal sensitization facilitating the onset of chronic pain attacks, including migraine. Recurrent headache attacks might establish a chronic neuroinflammatory ganglion profile contributing to the hypersensitive phenotype. Since it is ...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/1471-2202-13-143

    authors: Franceschini A,Nair A,Bele T,van den Maagdenberg AM,Nistri A,Fabbretti E

    更新日期:2012-11-21 00:00:00

  • Effects of dietary Na+ deprivation on epithelial Na+ channel (ENaC), BDNF, and TrkB mRNA expression in the rat tongue.

    abstract:BACKGROUND:In rodents, dietary Na+ deprivation reduces gustatory responses of primary taste fibers and central taste neurons to lingual Na+ stimulation. However, in the rat taste bud cells Na+ deprivation increases the number of amiloride sensitive epithelial Na+ channels (ENaC), which are considered as the "receptor" ...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/1471-2202-10-19

    authors: Huang T,Stähler F

    更新日期:2009-03-12 00:00:00

  • Factors that regulate embryonic gustatory development.

    abstract::Numerous molecular factors orchestrate the development of the peripheral taste system. The unique anatomy/function of the taste system makes this system ideal for understanding the mechanisms by which these factors function; yet the taste system is underutilized for this role. This review focuses on some of the many f...

    journal_title:BMC neuroscience

    pub_type: 杂志文章,评审

    doi:10.1186/1471-2202-8-S3-S4

    authors: Krimm RF

    更新日期:2007-09-18 00:00:00

  • Both 5' and 3' flanks regulate Zebrafish brain-derived neurotrophic factor gene expression.

    abstract:BACKGROUND:Precise control of developmental and cell-specific expression of the brain-derived neurotrophic factor (BDNF) gene is essential for normal neuronal development and the diverse functions of BDNF in the adult organism. We previously showed that the zebrafish BDNF gene has multiple promoters. The complexity of ...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/1471-2202-5-19

    authors: Heinrich G,Pagtakhan CJ

    更新日期:2004-05-21 00:00:00

  • Tissue sparing, behavioral recovery, supraspinal axonal sparing/regeneration following sub-acute glial transplantation in a model of spinal cord contusion.

    abstract:BACKGROUND:It has been shown that olfactory ensheathing glia (OEG) and Schwann cell (SCs) transplantation are beneficial as cellular treatments for spinal cord injury (SCI), especially acute and sub-acute time points. In this study, we transplanted DsRED transduced adult OEG and SCs sub-acutely (14 days) following a T1...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/1471-2202-14-106

    authors: Barbour HR,Plant CD,Harvey AR,Plant GW

    更新日期:2013-09-27 00:00:00

  • Gamma oscillation underlies hyperthermia-induced epileptiform-like spikes in immature rat hippocampal slices.

    abstract:BACKGROUND:Recently a hyperthermic rat hippocampal slice model system has been used to investigate febrile seizure pathophysiology. Our previous data indicates that heating immature rat hippocampal slices from 34 to 41 degrees C in an interface chamber induced epileptiform-like population spikes accompanied by a spread...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/1471-2202-2-18

    authors: Wu J,Javedan SP,Ellsworth K,Smith K,Fisher RS

    更新日期:2001-01-01 00:00:00

  • Evidence for inflammation-mediated memory dysfunction in gastropods: putative PLA2 and COX inhibitors abolish long-term memory failure induced by systemic immune challenges.

    abstract:BACKGROUND:Previous studies associate lipid peroxidation with long-term memory (LTM) failure in a gastropod model (Lymnaea stagnalis) of associative learning and memory. This process involves activation of Phospholipase A2 (PLA2), an enzyme mediating the release of fatty acids such as arachidonic acid that form the pre...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/1471-2202-14-83

    authors: Hermann PM,Park D,Beaulieu E,Wildering WC

    更新日期:2013-08-06 00:00:00

  • Acute stress alters transcript expression pattern and reduces processing of proBDNF to mature BDNF in Dicentrarchus labrax.

    abstract:BACKGROUND:Stress involves alterations of brain functioning that may precipitate to mood disorders. The neurotrophin Brain Derived Neurotrophic Factor (BDNF) has recently been involved in stress-induced adaptation. BDNF is a key regulator of neuronal plasticity and adaptive processes. Regulation of BDNF is complex and ...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/1471-2202-11-4

    authors: Tognoli C,Rossi F,Di Cola F,Baj G,Tongiorgi E,Terova G,Saroglia M,Bernardini G,Gornati R

    更新日期:2010-01-14 00:00:00

  • Colocalization of connexin 36 and corticotropin-releasing hormone in the mouse brain.

    abstract:BACKGROUND:Gap junction proteins, connexins, are expressed in most endocrine and exocrine glands in the body and are at least in some glands crucial for the hormonal secretion. To what extent connexins are expressed in neurons releasing hormones or neuropeptides from or within the central nervous system is, however, un...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/1471-2202-10-41

    authors: Westberg L,Sawa E,Wang AY,Gunaydin LA,Ribeiro AC,Pfaff DW

    更新日期:2009-04-30 00:00:00

  • Proximity ligation assay reveals both pre- and postsynaptic localization of the APP-processing enzymes ADAM10 and BACE1 in rat and human adult brain.

    abstract:BACKGROUND:Synaptic degeneration and accumulation of amyloid β-peptides (Aβ) are hallmarks of the Alzheimer diseased brain. Aβ is synaptotoxic and produced by sequential cleavage of the amyloid precursor protein (APP) by the β-secretase BACE1 and by γ-secretase. If APP is instead cleaved by the α-secretase ADAM10, Aβ w...

    journal_title:BMC neuroscience

    pub_type: 杂志文章

    doi:10.1186/s12868-020-0554-0

    authors: Lundgren JL,Vandermeulen L,Sandebring-Matton A,Ahmed S,Winblad B,Di Luca M,Tjernberg LO,Marcello E,Frykman S

    更新日期:2020-02-04 00:00:00