The Experts below are selected from a list of 1422 Experts worldwide ranked by ideXlab platform
Trevor G. Smart - One of the best experts on this subject based on the ideXlab platform.
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Constructing inhibitory synapses
Nature Reviews Neuroscience, 2001Co-Authors: Stephen J. Moss, Trevor G. SmartAbstract:Control of Nerve-Cell Excitability is crucial for normal brain function. Two main groups of inhibitory neurotransmitter receptors — GABA_A and glycine receptors — fulfil a significant part of this role. To mediate fast synaptic inhibition effectively, these receptors need to be localized and affixed opposite Nerve terminals that release the appropriate neurotransmitter at multiple sites on postsynaptic neurons. But for this to occur, neurons require intraCellular anchoring molecules, as well as mechanisms that ensure the efficient turnover and transport of mature, functional inhibitory synaptic receptor proteins. This review describes the dynamic regulation of synaptic GABA_A and glycine receptors and discusses recent advances in this rapidly evolving field. Synaptic targeting and clustering of GABA (γ-aminobutyric acid)and glycine receptors is mediated by the interaction of these receptor subunits with the cytoskeleton. The intraCellular domains of individual receptor subunits can interact with several proteins, including cytoskeletal elements, microtubule-binding proteins, neurotransmitter transporters, protein kinases, kinase-anchoring proteins and other signalling molecules. The roles of these protein–protein interactions in the synaptic accumulation and functional modulation of GABA_A and glycine receptors have begun to be unravelled and constitute the focus of this review. The large number of GABA and glycine receptor subunits is responsible for the extensive heterogeneity of glycine and GABA_A receptor structure. In the case of GABA receptors, the presence of specific subunits in a given receptor subtype can determine receptor trafficking and subCellular localization. Several accessory proteins that facilitate the accumulation of GABA_A and glycine receptors at synaptic sites have been identified. In the case of glycine receptors, gephyrin is crucial for their clustering at synapses. Gephyrin can interact with several signalling proteins such as collybistin (a GDP–GTP exchange factor) and Raft1 (a protein involved in the control of translation). This raises the possibility that the action of gephyrin could also involve signal transduction and/or structural remodelling. However, the presence of these proteins at glycine synapses has yet to be definitively proven. There are at least two mechanisms for the synaptic clustering of these GABA_A receptors, one dependent and one independent on gephyrin. The components of the gephyrin-independent mechanism have remained elusive but dystrophin has been identified as one possible candidate. A protein known as GABARAP (GABA_A receptor-associated protein)can also interact with GABA_A receptor γ2 subunits. However, GABARAP is unlikely to have a role in synaptic clustering and might instead be relevant for intraCellular transport. GABA_C receptors interact both with MAP1B, a molecule capable of binding actin and tubulin, and Glyt1E/F, a novel variant of the glycine transporter. The selective binding of MAP1B to GABA_C but not to GABA_A receptors could help to explain the differential localization of these receptors in the retina. The dynamic regulation of inhibitory transmitter receptors has begun to be elucidated. GABA_A receptors undergo constitutive endocytosis and travel between synaptic sites and endosomal structures but the relevance of this process for synaptic inhibition remains unknown. GABA_A receptors are also phosphorylated by several protein kinases and can directly bind both protein kinase C (PKC) and PKC-anchoring proteins. PKC can phosphorylate individual β subunits and thereby modulate GABA_A receptor function.
Stephen J. Moss - One of the best experts on this subject based on the ideXlab platform.
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Constructing inhibitory synapses
Nature Reviews Neuroscience, 2001Co-Authors: Stephen J. Moss, Trevor G. SmartAbstract:Control of Nerve-Cell Excitability is crucial for normal brain function. Two main groups of inhibitory neurotransmitter receptors — GABA_A and glycine receptors — fulfil a significant part of this role. To mediate fast synaptic inhibition effectively, these receptors need to be localized and affixed opposite Nerve terminals that release the appropriate neurotransmitter at multiple sites on postsynaptic neurons. But for this to occur, neurons require intraCellular anchoring molecules, as well as mechanisms that ensure the efficient turnover and transport of mature, functional inhibitory synaptic receptor proteins. This review describes the dynamic regulation of synaptic GABA_A and glycine receptors and discusses recent advances in this rapidly evolving field. Synaptic targeting and clustering of GABA (γ-aminobutyric acid)and glycine receptors is mediated by the interaction of these receptor subunits with the cytoskeleton. The intraCellular domains of individual receptor subunits can interact with several proteins, including cytoskeletal elements, microtubule-binding proteins, neurotransmitter transporters, protein kinases, kinase-anchoring proteins and other signalling molecules. The roles of these protein–protein interactions in the synaptic accumulation and functional modulation of GABA_A and glycine receptors have begun to be unravelled and constitute the focus of this review. The large number of GABA and glycine receptor subunits is responsible for the extensive heterogeneity of glycine and GABA_A receptor structure. In the case of GABA receptors, the presence of specific subunits in a given receptor subtype can determine receptor trafficking and subCellular localization. Several accessory proteins that facilitate the accumulation of GABA_A and glycine receptors at synaptic sites have been identified. In the case of glycine receptors, gephyrin is crucial for their clustering at synapses. Gephyrin can interact with several signalling proteins such as collybistin (a GDP–GTP exchange factor) and Raft1 (a protein involved in the control of translation). This raises the possibility that the action of gephyrin could also involve signal transduction and/or structural remodelling. However, the presence of these proteins at glycine synapses has yet to be definitively proven. There are at least two mechanisms for the synaptic clustering of these GABA_A receptors, one dependent and one independent on gephyrin. The components of the gephyrin-independent mechanism have remained elusive but dystrophin has been identified as one possible candidate. A protein known as GABARAP (GABA_A receptor-associated protein)can also interact with GABA_A receptor γ2 subunits. However, GABARAP is unlikely to have a role in synaptic clustering and might instead be relevant for intraCellular transport. GABA_C receptors interact both with MAP1B, a molecule capable of binding actin and tubulin, and Glyt1E/F, a novel variant of the glycine transporter. The selective binding of MAP1B to GABA_C but not to GABA_A receptors could help to explain the differential localization of these receptors in the retina. The dynamic regulation of inhibitory transmitter receptors has begun to be elucidated. GABA_A receptors undergo constitutive endocytosis and travel between synaptic sites and endosomal structures but the relevance of this process for synaptic inhibition remains unknown. GABA_A receptors are also phosphorylated by several protein kinases and can directly bind both protein kinase C (PKC) and PKC-anchoring proteins. PKC can phosphorylate individual β subunits and thereby modulate GABA_A receptor function.
A. N. Shalygin - One of the best experts on this subject based on the ideXlab platform.
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Influence of weakened constant magnetic field on Nerve Cell Excitability
Biophysics, 2008Co-Authors: S. M. Novikov, G. V. Maksimov, V. V. Volkov, A. N. ShalyginAbstract:Attenuation of the constant magnetic field by a factor of 200–250 (to ∼0.2 μT) raised the excitation threshold and decreased the amplitude of the action potentials in the isolated frog sciatic Nerve, and altered the conformation of carotenoids in the plasma membrane (sciatic axolemma) as well as in intraCellular vesicles (cytosomes of snail ganglia). The variation in Nerve Excitability was supposedly caused by changes in the ordering of membrane lipids.
S. M. Novikov - One of the best experts on this subject based on the ideXlab platform.
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Influence of weakened constant magnetic field on Nerve Cell Excitability
Biophysics, 2008Co-Authors: S. M. Novikov, G. V. Maksimov, V. V. Volkov, A. N. ShalyginAbstract:Attenuation of the constant magnetic field by a factor of 200–250 (to ∼0.2 μT) raised the excitation threshold and decreased the amplitude of the action potentials in the isolated frog sciatic Nerve, and altered the conformation of carotenoids in the plasma membrane (sciatic axolemma) as well as in intraCellular vesicles (cytosomes of snail ganglia). The variation in Nerve Excitability was supposedly caused by changes in the ordering of membrane lipids.
Sb Ras - One of the best experts on this subject based on the ideXlab platform.
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The Protein-Protein Interaction Networks of Dendritic Spines in the Early Phase of Long-Term Potentiation
Journal of Computer Science & Systems Biology, 2014Co-Authors: Anna L. Proskura, Aleksander S Ratushnyak, Tatyana A. Zapara, Sb RasAbstract:The neuron is a basic element of brain networks. Changes of Nerve Cell Excitability, the conduction of excitation, synaptic memory-forming in the case of the temporal coincidence of synaptic events are the obvious functions of the neuron - element of brain networks. The implementation of the neuron function depends on actions of its numerous molecular systems. The generalization of the complex processes of emergence of synaptic memory, that occur even in separate neuronal compartments, without special tools is a difficult, if at all possible, task. A technology that combines the creation of databases (elements and their relationships) with a visual representation in the form of networks facilitates this process. The developed protein-protein interaction network in dendritic spines of hippocampal pyramidal neurons facilitates the synthesis of numerous experimental data in conceptual knowledge about the principles and molecular mechanisms of neurons functioning.