The Experts below are selected from a list of 201 Experts worldwide ranked by ideXlab platform
Peter Csermely - One of the best experts on this subject based on the ideXlab platform.
-
synaptic polarity and sign balance prediction using gene expression data in the caenorhabditis elegans Chemical Synapse neuronal connectome network
PLOS Computational Biology, 2020Co-Authors: Bank G Fenyves, Gabor S Szilagyi, Zsolt Vassy, Csaba Sőti, Peter CsermelyAbstract:Graph theoretical analyses of nervous systems usually omit the aspect of connection polarity, due to data insufficiency. The Chemical Synapse network of Caenorhabditis elegans is a well-reconstructed directed network, but the signs of its connections are yet to be elucidated. Here, we present the gene expression-based sign prediction of the ionotropic Chemical Synapse connectome of C. elegans (3,638 connections and 20,589 Synapses total), incorporating available presynaptic neurotransmitter and postsynaptic receptor gene expression data for three major neurotransmitter systems. We made predictions for more than two-thirds of these Chemical Synapses and observed an excitatory-inhibitory (E:I) ratio close to 4:1 which was found similar to that observed in many real-world networks. Our open source tool (http://EleganSign.linkgroup.hu) is simple but efficient in predicting polarities by integrating neuronal connectome and gene expression data.
-
synaptic polarity and sign balance prediction using gene expression data in the caenorhabditis elegans Chemical Synapse neuronal connectome network
bioRxiv, 2020Co-Authors: Bank G Fenyves, Gabor S Szilagyi, Vassy Zsolt, Sőti Csaba, Peter CsermelyAbstract:Graph theoretical analyses of nervous systems usually omit the aspect of connection polarity, due to data insufficiency. The Chemical Synapse network of Caenorhabditis elegans is a well-reconstructed directed network, but the signs of its connections are yet to be elucidated. Here, we present the gene expression-based sign prediction of the C. elegans connectome, incorporating presynaptic neurotransmitter and postsynaptic receptor gene expression data (3,638 connections and 20,589 Synapses total). We made successful predictions for more than two-thirds of all Chemical Synapses and determined a ratio of excitatory-inhibitory (E:I) interneuronal ionotropic Chemical connections close to 4:1 which was found similar to that observed in many real-world networks. Our open source tool ( http://EleganSign.linkgroup.hu ) is simple but efficient in predicting polarities by integrating neuronal connectome and gene expression data.
Nigel Unwin - One of the best experts on this subject based on the ideXlab platform.
-
Segregation of lipids near acetylcholine-receptor channels imaged by cryo-EM
International Union of Crystallography, 2017Co-Authors: Nigel UnwinAbstract:Rapid communication at the Chemical Synapse depends on the action of ion channels residing in the postsynaptic membrane. The channels open transiently upon the binding of a neurotransmitter released from the presynaptic nerve terminal, eliciting an electrical response. Membrane lipids also play a vital but poorly understood role in this process of synaptic transmission. The present study examines the lipid distribution around nicotinic acetylcholine (ACh) receptors in tubular vesicles made from postsynaptic membranes of the Torpedo ray, taking advantage of the recent advances in cryo-EM. A segregated distribution of lipid molecules is found in the outer leaflet of the bilayer. Apparent cholesterol-rich patches are located in specific annular regions next to the transmembrane helices and also in a more extended `microdomain' between the apposed δ subunits of neighbouring receptors. The particular lipid distribution can be interpreted straightforwardly in relation to the gating movements revealed by an earlier time-resolved cryo-EM study, in which the membranes were exposed briefly to ACh. The results suggest that in addition to stabilizing the protein, cholesterol may play a mechanical role by conferring local rigidity to the membrane so that there is productive coupling between the extracellular and membrane domains, leading to opening of the channel
-
nicotinic acetylcholine receptor at 9 a resolution
Journal of Molecular Biology, 1993Co-Authors: Nigel UnwinAbstract:Abstract The nicotinic acetylcholine receptor is a cation-selective, ligand-gated ion channel, involved in signal transmission at the Chemical Synapse. This paper reports the three-dimensional appearance of the channel in the closed conformation, at 9 A resolution. The structure was determined by electron microscopy of tubular crystals of Torpedo postsynaptic membranes embedded in amorphous ice. The analysis was carried out by averaging data from separate images, using helical diffraction methods. The images were recorded over a wide range of defocus (7000 to 18,800 A) so that all spacings in the object were well sampled. Tubes of only one kind ((- 16,6) helical family) were processed, so that the Fourier terms could be averaged directly in reciprocal space. The three-dimensional map, obtained from 26 images, resolves some elements of secondary structure within the five protein subunits. In the synaptic part of each subunit, about 30 A from the bilayer surface, there is a group of three rods that are oriented predominantly perpendicular to the plane of the bilayer and twist around each other as in left-handed coil. These rods presumably are α-helices. Two of them line the entrance to the channel, and he third is on the outside. The distinctive appearance of the α subunits in this region suggests that the rods may be involved in forming the binding pocket for acetylcholine. In the bilayer-spanning part of each subunits there is only one rod clearly visible, which forms the wall lining the pore, and so is assumed to be the transmembrane helix, M2. This rod does not form a straight path through the lipid bilayer, but bends, or kinks, near its mid-point, where it is closest to the axis of the pore, and tilts radially outward on either side. It is flanked on the lipid-facing sides by a continuous rim of density, which seems likely to be composed of β-sheet. A tentative alignment is made between the three-dimensional densities and the sequence of M2, based on correlation of the appearance of the rods with a special pattern of amino acid residues in the sequence. This alignment places the charged groups at the ends of M2 symmetrically on either side of the bilayer, and a highly conserved leucine residue (Leu251 of the α subunit) at the level of the kink. It is suggested that luecine side-chains projecting into the pore from the kink associate and create a tight hydrophobic ring, which closes the channel by making a barrier that hydrated ions cannot cross.
-
nicotinic acetylcholine receptor at 9 a resolution
Journal of Molecular Biology, 1993Co-Authors: Nigel UnwinAbstract:The nicotinic acetylcholine receptor is a cation-selective, ligand-gated ion channel, involved in signal transmission at the Chemical Synapse. This paper reports the three-dimensional appearance of the channel in the closed conformation, at 9 A resolution. The structure was determined by electron microscopy of tubular crystals of Torpedo postsynaptic membranes embedded in amorphous ice. The analysis was carried out by averaging data from separate images, using helical diffraction methods. The images were recorded over a wide range of defocus (7000 to 18,800 A) so that all spacings in the object were well sampled. Tubes of only one kind ((-16.6) helical family) were processed, so that the Fourier terms could be averaged directly in reciprocal space. The three-dimensional map, obtained from 26 images, resolves some elements of secondary structure within the five protein subunits. In the synaptic part of each subunit, about 30 A from the bilayer surface, there is a group of three rods that are oriented predominantly perpendicular to the plane of the bilayer and twist around each other as in a left-handed coil. These rods presumably are alpha-helices. Two of them line the entrance to the channel, and the third is on the outside. The distinctive appearance of the alpha subunits in this region suggests that the rods may be involved in forming the binding pocket for acetylcholine. In the bilayer-spanning part of each subunit there is only one rod clearly visible, which forms the wall lining the pore, and so is assumed to be the transmembrane helix, M2. This rod does not form a straight path through the lipid bilayer, but bends, or kinks, near its mid-point, where it is closest to the axis of the pore, and tilts radially outwards on either side. It is flanked on the lipid-facing sides by a continuous rim of density, which seems likely to be composed of beta-sheet. A tentative alignment is made between the three-dimensional densities and the sequence of M2, based on correlation of the appearance of the rods with a special pattern of amino acid residues in the sequence. This alignment places the charged groups at the ends of M2 symmetrically on either side of the bilayer, and a highly conserved leucine residue (Leu251 of the alpha subunit) at the level of the kink.(ABSTRACT TRUNCATED AT 400 WORDS)
Bank G Fenyves - One of the best experts on this subject based on the ideXlab platform.
-
synaptic polarity and sign balance prediction using gene expression data in the caenorhabditis elegans Chemical Synapse neuronal connectome network
PLOS Computational Biology, 2020Co-Authors: Bank G Fenyves, Gabor S Szilagyi, Zsolt Vassy, Csaba Sőti, Peter CsermelyAbstract:Graph theoretical analyses of nervous systems usually omit the aspect of connection polarity, due to data insufficiency. The Chemical Synapse network of Caenorhabditis elegans is a well-reconstructed directed network, but the signs of its connections are yet to be elucidated. Here, we present the gene expression-based sign prediction of the ionotropic Chemical Synapse connectome of C. elegans (3,638 connections and 20,589 Synapses total), incorporating available presynaptic neurotransmitter and postsynaptic receptor gene expression data for three major neurotransmitter systems. We made predictions for more than two-thirds of these Chemical Synapses and observed an excitatory-inhibitory (E:I) ratio close to 4:1 which was found similar to that observed in many real-world networks. Our open source tool (http://EleganSign.linkgroup.hu) is simple but efficient in predicting polarities by integrating neuronal connectome and gene expression data.
-
synaptic polarity and sign balance prediction using gene expression data in the caenorhabditis elegans Chemical Synapse neuronal connectome network
bioRxiv, 2020Co-Authors: Bank G Fenyves, Gabor S Szilagyi, Vassy Zsolt, Sőti Csaba, Peter CsermelyAbstract:Graph theoretical analyses of nervous systems usually omit the aspect of connection polarity, due to data insufficiency. The Chemical Synapse network of Caenorhabditis elegans is a well-reconstructed directed network, but the signs of its connections are yet to be elucidated. Here, we present the gene expression-based sign prediction of the C. elegans connectome, incorporating presynaptic neurotransmitter and postsynaptic receptor gene expression data (3,638 connections and 20,589 Synapses total). We made successful predictions for more than two-thirds of all Chemical Synapses and determined a ratio of excitatory-inhibitory (E:I) interneuronal ionotropic Chemical connections close to 4:1 which was found similar to that observed in many real-world networks. Our open source tool ( http://EleganSign.linkgroup.hu ) is simple but efficient in predicting polarities by integrating neuronal connectome and gene expression data.
Gabor S Szilagyi - One of the best experts on this subject based on the ideXlab platform.
-
synaptic polarity and sign balance prediction using gene expression data in the caenorhabditis elegans Chemical Synapse neuronal connectome network
PLOS Computational Biology, 2020Co-Authors: Bank G Fenyves, Gabor S Szilagyi, Zsolt Vassy, Csaba Sőti, Peter CsermelyAbstract:Graph theoretical analyses of nervous systems usually omit the aspect of connection polarity, due to data insufficiency. The Chemical Synapse network of Caenorhabditis elegans is a well-reconstructed directed network, but the signs of its connections are yet to be elucidated. Here, we present the gene expression-based sign prediction of the ionotropic Chemical Synapse connectome of C. elegans (3,638 connections and 20,589 Synapses total), incorporating available presynaptic neurotransmitter and postsynaptic receptor gene expression data for three major neurotransmitter systems. We made predictions for more than two-thirds of these Chemical Synapses and observed an excitatory-inhibitory (E:I) ratio close to 4:1 which was found similar to that observed in many real-world networks. Our open source tool (http://EleganSign.linkgroup.hu) is simple but efficient in predicting polarities by integrating neuronal connectome and gene expression data.
-
synaptic polarity and sign balance prediction using gene expression data in the caenorhabditis elegans Chemical Synapse neuronal connectome network
bioRxiv, 2020Co-Authors: Bank G Fenyves, Gabor S Szilagyi, Vassy Zsolt, Sőti Csaba, Peter CsermelyAbstract:Graph theoretical analyses of nervous systems usually omit the aspect of connection polarity, due to data insufficiency. The Chemical Synapse network of Caenorhabditis elegans is a well-reconstructed directed network, but the signs of its connections are yet to be elucidated. Here, we present the gene expression-based sign prediction of the C. elegans connectome, incorporating presynaptic neurotransmitter and postsynaptic receptor gene expression data (3,638 connections and 20,589 Synapses total). We made successful predictions for more than two-thirds of all Chemical Synapses and determined a ratio of excitatory-inhibitory (E:I) interneuronal ionotropic Chemical connections close to 4:1 which was found similar to that observed in many real-world networks. Our open source tool ( http://EleganSign.linkgroup.hu ) is simple but efficient in predicting polarities by integrating neuronal connectome and gene expression data.
Ernest M Wright - One of the best experts on this subject based on the ideXlab platform.
-
conical electron tomography of a Chemical Synapse polyhedral cages dock vesicles to the active zone
The Journal of Neuroscience, 2008Co-Authors: Guido A Zampighi, N Fain, Lorenzo Zampighi, Francesca Cantele, Salvatore Lanzavecchia, Ernest M WrightAbstract:In this study, we tested the hypothesis that the structure of the active zone of Chemical Synapses has remained uncertain because of limitations of conventional electron microscopy. To resolve these limitations, we reconstructed Chemical Synapses of rat neocortex, the archetypical “average” Synapse, by conical electron tomography, a method that exhibits an isotropic in plane resolution of ∼3 nm and eliminates the need to impose symmetry or use averaging methods to increase signal-to-noise ratios. Analysis of 17 reconstructions by semiautomatic density segmentation indicated that the active zone was constructed of a variable number of distinct “synaptic units” comprising a polyhedral cage and a corona of approximately seven vesicles. The polyhedral cages measured ∼60 nm in diameter, with a density of ∼44/μm2 and were associated with vesicles at the active zone (“first tier”). Vesicles in this first-tier position represented ∼7.5% of the total number of vesicles in the terminal and were contiguous, hemifused (∼4% of total), or fully fused (∼0.5% of total) to the plasma membrane. Our study supports the hypothesis that rat neocortical Synapses are constructed of variable numbers of distinct synaptic units that facilitate the docking of vesicles to the active zone and determine the number of vesicles available for immediate release.
-
conical electron tomography of a Chemical Synapse vesicles docked to the active zone are hemi fused
Biophysical Journal, 2006Co-Authors: Guido A Zampighi, N Fain, Lorenzo Zampighi, Salvatore Lanzavecchia, Sidney A Simon, Ernest M WrightAbstract:We have used thin sectioning and conical electron tomography to determine the three-dimensional structure of synaptic vesicles that were associated (docked) at release sites of the presynaptic membrane, called active-zones. Vesicles docked at the active zone occupied a strategic location: they formed regions of contact with the plasma membrane on one side and with that of one or more vesicles located deeper within the presynaptic terminal on the other side. The region of contact with the active zone measured ∼15 nm in diameter (∼2% of the vesicle's surface) and contained a smaller ∼6 nm region where the proximal leaflets merged (hemi-fused). Hemi-fusion was only observed on the side of vesicles in contact with the active zone; at the side of contact between neighboring vesicles, the membranes were not hemi-fused. Approximately three-fourths of the docked vesicles contained hemi-fused regions. Vesicles fully fused to the active zone (exhibiting pores that appeared as interruptions of a single membrane) were less frequently observed (∼1 of 10 hemi-fused vesicles). In conclusion, our observations in cortical Synapses strengthen the hypothesis that hemi-fusion is a stable intermediary that precedes full fusion and release.