Structural basis of the different gating kinetics of fetal and adult acetylcholine receptors.


:Structure-function studies have identified key functional motifs in the acetylcholine receptor, including residues that contribute to the ion channel and to the ligand-binding sites. Little is known, however, about determinants of channel gating kinetics. To identify structural correlates of gating, we examined the structural basis of the fetal-to-adult decrease in channel open time conferred by the presence of the epsilon subunit in place of the gamma subunit. By constructing chimeras composed of segments of the epsilon and gamma subunits, we show that the main determinant of this kinetic change is a 30 residue segment of a predicted amphipathic helix located between transmembrane domains M3 and M4. Further subdividing the amphipathic helix revealed that either multiple residues or its overall conformation confers this regulation of channel kinetics. We also show that L440 and M442, conserved residues within M4 of the gamma subunit, contribute to long duration openings characteristic of the fetal receptor.






Bouzat C,Bren N,Sine SM




Has Abstract


1994-12-01 00:00:00
















  • Charybdotoxin binding in the I(Ks) pore demonstrates two MinK subunits in each channel complex.

    abstract::I(Ks) voltage-gated K(+) channels contain four pore-forming KCNQ1 subunits and MinK accessory subunits in a number that has been controversial. Here, I(Ks) channels assembled naturally by monomer subunits are compared to those with linked subunits that force defined stoichiometries. Two strategies that exploit charybd...


    pub_type: 杂志文章


    authors: Chen H,Kim LA,Rajan S,Xu S,Goldstein SA

    更新日期:2003-09-25 00:00:00

  • Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary.

    abstract::Evolutionary conservation of members of the NGF family in vertebrates was studied by DNA sequence analysis of PCR fragments for NGF, BDNF, and NT-3 from human, rat, chicken, viper, Xenopus, salmon, and ray. The results showed that the three factors are highly conserved from fishes to mammals. Phylogenetic trees reflec...


    pub_type: 杂志文章


    authors: Hallböök F,Ibáñez CF,Persson H

    更新日期:1991-05-01 00:00:00

  • Hypocretin/Orexin excites hypocretin neurons via a local glutamate neuron-A potential mechanism for orchestrating the hypothalamic arousal system.

    abstract::Neurons that release hypocretin/orexin modulate sleep, arousal, and energy homeostasis; the absence of hypocretin results in narcolepsy. Here we present data on the physiological characteristics of these cells, identified with GFP in transgenic mouse brain slices. Hypocretin-1 and -2 depolarized hypocretin neurons by ...


    pub_type: 杂志文章


    authors: Li Y,Gao XB,Sakurai T,van den Pol AN

    更新日期:2002-12-19 00:00:00

  • Cellular clocks in AVP neurons of the SCN are critical for interneuronal coupling regulating circadian behavior rhythm.

    abstract::The suprachiasmatic nucleus (SCN), the primary circadian pacemaker in mammals, is a network structure composed of multiple types of neurons. Here, we report that mice with a Bmal1 deletion specific to arginine vasopressin (AVP)-producing neurons showed marked lengthening in the free-running period and activity time of...


    pub_type: 杂志文章


    authors: Mieda M,Ono D,Hasegawa E,Okamoto H,Honma K,Honma S,Sakurai T

    更新日期:2015-03-04 00:00:00

  • Neuropilin-2/PlexinA3 Receptors Associate with GluA1 and Mediate Sema3F-Dependent Homeostatic Scaling in Cortical Neurons.

    abstract::Regulation of AMPA-type glutamate receptor (AMPAR) number at synapses is a major mechanism for controlling synaptic strength during homeostatic scaling in response to global changes in neural activity. We show that the secreted guidance cue semaphorin 3F (Sema3F) and its neuropilin-2 (Npn-2)/plexinA3 (PlexA3) holorece...


    pub_type: 杂志文章


    authors: Wang Q,Chiu SL,Koropouli E,Hong I,Mitchell S,Easwaran TP,Hamilton NR,Gustina AS,Zhu Q,Ginty DD,Huganir RL,Kolodkin AL

    更新日期:2017-12-06 00:00:00

  • Light-induced plasticity of synaptic AMPA receptor composition in retinal ganglion cells.

    abstract::Light-evoked responses of all three major classes of retinal ganglion cells (RGCs) are mediated by NMDA receptors (NMDARs) and AMPA receptors (AMPARs). Although synaptic activity at RGC synapses is highly dynamic, synaptic plasticity has not been observed in adult RGCs. Here, using patch-clamp recordings in dark-adapt...


    pub_type: 杂志文章


    authors: Jones RS,Carroll RC,Nawy S

    更新日期:2012-08-09 00:00:00

  • MicroRNA 135 is essential for chronic stress resiliency, antidepressant efficacy, and intact serotonergic activity.

    abstract::The link between dysregulated serotonergic activity and depression and anxiety disorders is well established, yet the molecular mechanisms underlying these psychopathologies are not fully understood. Here, we explore the role of microRNAs in regulating serotonergic (5HT) neuron activity. To this end, we determined the...


    pub_type: 杂志文章


    authors: Issler O,Haramati S,Paul ED,Maeno H,Navon I,Zwang R,Gil S,Mayberg HS,Dunlop BW,Menke A,Awatramani R,Binder EB,Deneris ES,Lowry CA,Chen A

    更新日期:2014-07-16 00:00:00

  • Hypoxia enhances S-nitrosylation-mediated NMDA receptor inhibition via a thiol oxygen sensor motif.

    abstract::Under ambient air conditions, NO inhibits NMDAR activity by reacting with the NR2A subunit C399 along with two additional cysteine pairs if their disulfide bonds are reduced to free thiol groups [NR1(C744,C798); NR2(C87,C320)]. Here we demonstrate that relative hypoxia enhances S-nitrosylation of NMDARs by a unique me...


    pub_type: 杂志文章


    authors: Takahashi H,Shin Y,Cho SJ,Zago WM,Nakamura T,Gu Z,Ma Y,Furukawa H,Liddington R,Zhang D,Tong G,Chen HS,Lipton SA

    更新日期:2007-01-04 00:00:00

  • Developmental regulation of neuronal K+ channels by target-derived TGF beta in vivo and in vitro.

    abstract::The functional expression of Ca2+-activated K+ channels (KCa) in developing chick ciliary ganglion (CG) neurons requires interactions with target tissues and preganglionic innervation. Here, we show that the stimulatory effects of target tissues are mediated by an isoform of TGFbeta. Exposure of cultured CG neurons to...


    pub_type: 杂志文章


    authors: Cameron JS,Lhuillier L,Subramony P,Dryer SE

    更新日期:1998-11-01 00:00:00

  • TGF beta 2 and TGF beta 3 are potent survival factors for midbrain dopaminergic neurons.

    abstract::The vertebrate ventral midbrain contains 3-4 x 10(4) dopaminergic neurons that influence motor activity, emotional behavior, and cognition. Recently, glial cell line-derived neurotrophic factor (GDNF) was shown to be a potent survival factor for these dopaminergic neurons in culture. However, many midbrain dopaminergi...


    pub_type: 杂志文章


    authors: Poulsen KT,Armanini MP,Klein RD,Hynes MA,Phillips HS,Rosenthal A

    更新日期:1994-11-01 00:00:00

  • To think or not to think: synaptic activity and Abeta release.

    abstract::Accumulation of beta-amyloid protein (Abeta) in the extracellular space of the brain has been hypothesized to be a culprit in the pathogenesis of Alzheimer's disease. In this issue of Neuron, Cirrito et al. describe a series of experiments demonstrating that extracellular Abeta levels are directly modulated by neurona...


    pub_type: 评论,杂志文章,评审


    authors: Schroeder BE,Koo EH

    更新日期:2005-12-22 00:00:00

  • Does neuronal synchrony underlie visual feature grouping?

    abstract::Previous research suggests that synchronous neural activity underlies perceptual grouping of visual image features. The generality of this mechanism is unclear, however, as previous studies have focused on pairs of neurons with overlapping or collinear receptive fields. By sampling more broadly and employing stimuli t...


    pub_type: 杂志文章


    authors: Palanca BJ,DeAngelis GC

    更新日期:2005-04-21 00:00:00

  • Transcriptional Networks Controlled by NKX2-1 in the Development of Forebrain GABAergic Neurons.

    abstract::The embryonic basal ganglia generates multiple projection neurons and interneuron subtypes from distinct progenitor domains. Combinatorial interactions of transcription factors and chromatin are thought to regulate gene expression. In the medial ganglionic eminence, the NKX2-1 transcription factor controls regional id...


    pub_type: 杂志文章


    authors: Sandberg M,Flandin P,Silberberg S,Su-Feher L,Price JD,Hu JS,Kim C,Visel A,Nord AS,Rubenstein JLR

    更新日期:2016-09-21 00:00:00

  • A Central Move for CB2 Receptors.

    abstract::The function of the CB2 cannabinoid receptor in the brain has long been a matter of debate. In this issue of Neuron, Stempel et al. (2016) describe a mechanism whereby endocannabinoid production leads to a cell-intrinsic hyperpolarization that controls self activity. ...


    pub_type: 评论,杂志文章,评审


    authors: Quraishi SA,Paladini CA

    更新日期:2016-05-18 00:00:00

  • Orientation preference patterns in mammalian visual cortex: a wire length minimization approach.

    abstract::In the visual cortex of many mammals, orientation preference changes smoothly along the cortical surface, with the exception of singularities such as pinwheels and fractures. The reason for the existence of these singularities has remained elusive, suggesting that they are developmental artifacts. We show that singula...


    pub_type: 杂志文章


    authors: Koulakov AA,Chklovskii DB

    更新日期:2001-02-01 00:00:00

  • Crystal structures of the GluR5 and GluR6 ligand binding cores: molecular mechanisms underlying kainate receptor selectivity.

    abstract::Little is known about the molecular mechanisms underlying differences in the ligand binding properties of AMPA, kainate, and NMDA subtype glutamate receptors. Crystal structures of the GluR5 and GluR6 kainate receptor ligand binding cores in complexes with glutamate, 2S,4R-4-methylglutamate, kainate, and quisqualate h...


    pub_type: 杂志文章


    authors: Mayer ML

    更新日期:2005-02-17 00:00:00

  • Intersecting circuits generate precisely patterned retinal waves.

    abstract::The developing retina generates spontaneous glutamatergic (stage III) waves of activity that sequentially recruit neighboring ganglion cells with opposite light responses (ON and OFF RGCs). This activity pattern is thought to help establish parallel ON and OFF pathways in downstream visual areas. The circuits that pro...


    pub_type: 杂志文章


    authors: Akrouh A,Kerschensteiner D

    更新日期:2013-07-24 00:00:00

  • Presynaptic miniature GABAergic currents in developing interneurons.

    abstract::Miniature synaptic currents have long been known to represent random transmitter release under resting conditions, but much remains to be learned about their nature and function in central synapses. In this work, we describe a new class of miniature currents ("preminis") that arise by the autocrine activation of axona...


    pub_type: 杂志文章


    authors: Trigo FF,Bouhours B,Rostaing P,Papageorgiou G,Corrie JE,Triller A,Ogden D,Marty A

    更新日期:2010-04-29 00:00:00

  • Characterization of the signaling interactions that promote the survival and growth of developing retinal ganglion cells in culture.

    abstract::The signaling mechanisms that control the survival of CNS neurons are poorly understood. Here we show that, in contrast to PNS neurons, the survival of purified postnatal rat retinal ganglion cells (RGCs) in vitro is not promoted by peptide trophic factors unless their intracellular cAMP is increased pharmacologically...


    pub_type: 杂志文章


    authors: Meyer-Franke A,Kaplan MR,Pfrieger FW,Barres BA

    更新日期:1995-10-01 00:00:00

  • An imbalancing act: gap junctions reduce the backward motor circuit activity to bias C. elegans for forward locomotion.

    abstract::A neural network can sustain and switch between different activity patterns to execute multiple behaviors. By monitoring the decision making for directional locomotion through motor circuit calcium imaging in behaving Caenorhabditis elegans (C. elegans), we reveal that C. elegans determines the directionality of movem...


    pub_type: 杂志文章


    authors: Kawano T,Po MD,Gao S,Leung G,Ryu WS,Zhen M

    更新日期:2011-11-17 00:00:00

  • Initiation of rhombomeric Hoxb4 expression requires induction by somites and a retinoid pathway.

    abstract::Anteroposterior (AP) patterning in the vertebrate hindbrain is dependent upon the establishment of segmental domains of Hox expression. We investigated the mechanism that governs the early expression of Hoxb4 and found that transient signaling from the paraxial mesoderm induces expression in the hindbrain. Induction i...


    pub_type: 杂志文章


    authors: Gould A,Itasaki N,Krumlauf R

    更新日期:1998-07-01 00:00:00

  • A role for proteoglycans in the guidance of a subset of pioneer axons in cultured embryos of the cockroach.

    abstract::Several molecules involved in the development of the nervous system have specific binding sites for the glycosaminoglycan (GAG) side chains of proteoglycans. Exogenous GAGs should bind to these sites, competitively inhibit interactions with proteoglycans, and perturb development. GAGs added to the culture medium pertu...


    pub_type: 杂志文章


    authors: Wang L,Denburg JL

    更新日期:1992-04-01 00:00:00

  • Psychopathology and the human connectome: toward a transdiagnostic model of risk for mental illness.

    abstract::The panoply of cognitive, affective, motivational, and social functions that underpin everyday human experience requires precisely choreographed patterns of interaction between networked brain regions. Perhaps not surprisingly, diverse forms of psychopathology are characterized by breakdowns in these interregional rel...


    pub_type: 杂志文章,评审


    authors: Buckholtz JW,Meyer-Lindenberg A

    更新日期:2012-06-21 00:00:00

  • Ion Permeation and Mechanotransduction Mechanisms of Mechanosensitive Piezo Channels.

    abstract::Piezo proteins have been proposed as the long-sought-after mechanosensitive cation channels in mammals that play critical roles in various mechanotransduction processes. However, the molecular bases that underlie their ion permeation and mechanotransduction have remained functionally undefined. Here we report our find...


    pub_type: 杂志文章


    authors: Zhao Q,Wu K,Geng J,Chi S,Wang Y,Zhi P,Zhang M,Xiao B

    更新日期:2016-03-16 00:00:00

  • Curbing the excesses of youth: molecular insights into axonal pruning.

    abstract::The embryonic nervous system is refined over the course of development as a result of the twin processes of naturally occurring cell death and selective axon pruning. Recent studies provide new insights into the molecular events that underlie axon pruning and underscore the diversity of refinement processes employed b...


    pub_type: 评论,杂志文章,评审


    authors: Kantor DB,Kolodkin AL

    更新日期:2003-06-19 00:00:00

  • A putative vesicular transporter expressed in Drosophila mushroom bodies that mediates sexual behavior may define a neurotransmitter system.

    abstract::Vesicular transporters are required for the storage of all classical and amino acid neurotransmitters in synaptic vesicles. Some neurons lack known vesicular transporters, suggesting additional neurotransmitter systems remain unidentified. Insect mushroom bodies (MBs) are critical for several behaviors, including lear...


    pub_type: 杂志文章


    authors: Brooks ES,Greer CL,Romero-Calderón R,Serway CN,Grygoruk A,Haimovitz JM,Nguyen BT,Najibi R,Tabone CJ,de Belle JS,Krantz DE

    更新日期:2011-10-20 00:00:00

  • Making an effort to listen: mechanical amplification in the ear.

    abstract::The inner ear's performance is greatly enhanced by an active process defined by four features: amplification, frequency selectivity, compressive nonlinearity, and spontaneous otoacoustic emission. These characteristics emerge naturally if the mechanoelectrical transduction process operates near a dynamical instability...


    pub_type: 杂志文章,评审


    authors: Hudspeth AJ

    更新日期:2008-08-28 00:00:00

  • Excitement about inhibitory presynaptic terminals.

    abstract::Based on extrapolation from excitatory synapses, it is often assumed that depletion of the releasable pool of synaptic vesicles is the main factor underlying depression at inhibitory synapses. In this issue of Neuron, using subcellular patch-clamp recording from inhibitory presynaptic terminals, Kawaguchi and Sakaba (...


    pub_type: 评论,杂志文章


    authors: Vandael DH,Espinoza C,Jonas P

    更新日期:2015-03-18 00:00:00

  • Closing in on the resting state of the Shaker K(+) channel.

    abstract::Membrane depolarization causes voltage-gated ion channels to transition from a resting/closed conformation to an activated/open conformation. We used voltage-clamp fluorometry to measure protein motion at specific regions of the Shaker Kv channel. This enabled us to construct new structural models of the resting/close...


    pub_type: 杂志文章


    authors: Pathak MM,Yarov-Yarovoy V,Agarwal G,Roux B,Barth P,Kohout S,Tombola F,Isacoff EY

    更新日期:2007-10-04 00:00:00

  • Parkin and Hsp70 sacked by BAG5.

    abstract::Loss-of-function mutations in the parkin gene, which encodes an E3 ubiquitin ligase, are the major cause of early-onset Parkinson's disease (PD). In this issue of Neuron, Kalia et al. show that the bcl-2-associated athanogene 5 (BAG5) enhances dopamine neuron death in an in vivo model of PD through inhibiting the E3 l...


    pub_type: 评论,杂志文章,评审


    authors: Chung KK,Dawson TM

    更新日期:2004-12-16 00:00:00