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Microscopy Research and Technique Apr 2000Membrane skeletons, in particular the spectrin-based skeleton, are thought to participate in the organization of specialized membrane domains by restricting integral... (Review)
Review
Membrane skeletons, in particular the spectrin-based skeleton, are thought to participate in the organization of specialized membrane domains by restricting integral proteins to specific membrane sites. In the neuromuscular junction, discrete isoforms of spectrin and ankyrin, the peripheral protein that links spectrin to the membrane, colocalize with voltage-dependent sodium channels and N-CAM at the troughs of the postsynaptic membrane folds. Moreover, beta-spectrin, N-CAM, and sodium channels become clustered at the endplate during a period of time coincident with postsynaptic fold formation and synapse maturation. These observations suggest a role of the spectrin skeleton in directing and maintaining postsynaptic accumulations of sodium channels and N-CAM. In addition, the coexistence of spectrin and dystrophin at the troughs of the junctional folds raises the question of their respective functions in this membrane domain, where both cytoskeletal proteins have the potential to associate with sodium channels via ankyrin and syntrophin, respectively. Possible scenarios are discussed here with respect to accumulating evidence from studies of assembly of similar membrane domains in neurons.
Topics: Animals; Ankyrins; Neuromuscular Junction; Rats; Spectrin; Synaptic Membranes
PubMed: 10757883
DOI: 10.1002/(SICI)1097-0029(20000401)49:1<101::AID-JEMT11>3.0.CO;2-U -
Microscopy Research and Technique Apr 2000Many aspects of the organization of the electromotor synapse of electric fish resemble the nerve-muscle junction. In particular, the postsynaptic membrane in both... (Review)
Review
Many aspects of the organization of the electromotor synapse of electric fish resemble the nerve-muscle junction. In particular, the postsynaptic membrane in both systems share most of their proteins. As a remarquable source of cholinergic synapses, the Torpedo electrocyte model has served to identify the most important components involved in synaptic transmission such as the nicotinic acetylcholine receptor and the enzyme acetylcholinesterase, as well as proteins associated with the subsynaptic cytoskeleton and the extracellular matrix involved in the assembly of the postsynaptic membrane, namely the 43-kDa protein-rapsyn, the dystrophin/utrophin complex, agrin, and others. This review encompasses some representative experiments that helped to clarify essential aspects of the supramolecular organization and assembly of the postsynaptic apparatus of cholinergic synapses.
Topics: Animals; Cytoskeletal Proteins; Cytoskeleton; Dystrophin; Electric Organ; Membrane Proteins; Models, Biological; Muscle Proteins; Receptors, Nicotinic; Synaptic Membranes; Torpedo; Utrophin
PubMed: 10757880
DOI: 10.1002/(SICI)1097-0029(20000401)49:1<73::AID-JEMT8>3.0.CO;2-L -
The Journal of Neuroscience : the... Jan 2007Targeted membrane addition is a hallmark of many cellular functions. In the nervous system, modification of synaptic membrane size has a major impact on synaptic... (Comparative Study)
Comparative Study
Targeted membrane addition is a hallmark of many cellular functions. In the nervous system, modification of synaptic membrane size has a major impact on synaptic function. However, because of the complex shape of neurons and the need to target membrane addition to very small and polarized synaptic compartments, this process is poorly understood. Here, we show that Gtaxin (GTX), a Drosophila t-SNARE (target-soluble N-ethylmaleimide-sensitive factor attachment protein receptor), is required for expansion of postsynaptic membranes during new synapse formation. Mutations in gtx lead to drastic reductions in postsynaptic membrane surface, whereas gtx upregulation results in the formation of complex membrane structures at ectopic sites. Postsynaptic GTX activity depends on its direct interaction with Discs-Large (DLG), a multidomain scaffolding protein of the PSD-95 (postsynaptic density protein-95) family with key roles in cell polarity and formation of cellular junctions as well as synaptic protein anchoring and trafficking. We show that DLG selectively determines the postsynaptic distribution of GTX to type I, but not to type II or type III boutons on the same cell, thereby defining sites of membrane addition to this unique set of glutamatergic synapses. We provide a mechanistic explanation for selective targeted membrane expansion at specific synaptic junctions.
Topics: Amino Acid Sequence; Animals; Drosophila; Drosophila Proteins; Drug Resistance; Molecular Sequence Data; Presynaptic Terminals; SNARE Proteins; Synaptic Membranes; Tumor Suppressor Proteins
PubMed: 17267557
DOI: 10.1523/JNEUROSCI.3160-06.2007 -
Nature Mar 1976The postsynaptic actions of some neurotransmitters may be mediated through cyclic nucleotides and cyclic nucleotide-dependent phosphorylation of specific membrane... (Review)
Review
The postsynaptic actions of some neurotransmitters may be mediated through cyclic nucleotides and cyclic nucleotide-dependent phosphorylation of specific membrane proteins in postsynaptic cells. In addition to providing a molecular basis for the actions of several neurotransmitters and of certain drugs affecting behaviour, the model suggests a mechanism by which neurotransmitter signals may be converted into electrophysiological responses in postsynaptic cells.
Topics: Cyclic AMP; Cyclic GMP; Dopamine; Ganglia, Autonomic; Membranes; Models, Neurological; Muscle, Smooth; Nucleotides, Cyclic; Permeability; Phosphates; Proteins; Receptors, Drug; Synapses; Synaptic Transmission
PubMed: 176592
DOI: 10.1038/260101a0 -
Molecular and Cellular Neurosciences Apr 2007The postsynaptic density (PSD) is a structure composed of both membranous and cytoplasmic proteins localized at the postsynaptic plasma membrane of excitatory synapses.... (Review)
Review
The postsynaptic density (PSD) is a structure composed of both membranous and cytoplasmic proteins localized at the postsynaptic plasma membrane of excitatory synapses. Biochemical and molecular biological studies have identified a number of proteins present in the PSD. Glutamate receptors are important constituents of the PSD and membrane proteins involved in synaptic signal transduction and cell adhesion are also essential components. Scaffolding proteins containing multiple protein interaction motifs are thought to provide the framework of the PSD through their interactions with both membrane proteins and the cytoplasmic proteins. Among the cytoplasmic signaling molecules, calcium-calmodulin-dependent protein kinase II stands out as a major component of the PSD and its dynamic translocation to the PSD in response to neuronal activity is crucial in synaptic signal transduction. Recent advancements in molecular biological, structural and electrophysiological techniques have enabled us to directly measure the number, distribution and interactions of PSD molecules with high sensitivity and precision. In this review, I describe the structure and molecular composition of the PSD as well as the molecular interactions between the major constituents. This information will be combined with recent quantitative analyses of the PSD protein contents per synapse, in order to provide a current view of the PSD molecular architecture and its dynamics.
Topics: Animals; Brain; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases; Humans; Membrane Proteins; Nerve Tissue Proteins; Receptors, Glutamate; Synapses
PubMed: 17321751
DOI: 10.1016/j.mcn.2007.01.006 -
Journal of Visualized Experiments : JoVE Sep 2014Neuronal subcellular fractionation techniques allow the quantification of proteins that are trafficked to and from the synapse. As originally described in the late...
Neuronal subcellular fractionation techniques allow the quantification of proteins that are trafficked to and from the synapse. As originally described in the late 1960's, proteins associated with the synaptic plasma membrane can be isolated by ultracentrifugation on a sucrose density gradient. Once synaptic membranes are isolated, the macromolecular complex known as the post-synaptic density can be subsequently isolated due to its detergent insolubility. The techniques used to isolate synaptic plasma membranes and post-synaptic density proteins remain essentially the same after 40 years, and are widely used in current neuroscience research. This article details the fractionation of proteins associated with the synaptic plasma membrane and post-synaptic density using a discontinuous sucrose gradient. Resulting protein preparations are suitable for western blotting or 2D DIGE analysis.
Topics: Animals; Centrifugation, Density Gradient; Membrane Proteins; Mice; Nerve Tissue Proteins; Sucrose; Synaptic Membranes; Synaptosomes
PubMed: 25226023
DOI: 10.3791/51896 -
Neuroscience Jul 1983A method is described for the preparation of a subcellular fraction, 30-50% pure, of intact postsynaptic units from rat cerebral cortex. The isolation procedure is based...
A method is described for the preparation of a subcellular fraction, 30-50% pure, of intact postsynaptic units from rat cerebral cortex. The isolation procedure is based on chemical dissociation of the synaptic cleft as described by Crawford, Osborne & Potter followed by sonication of the extracted membranes and separation of the postsynaptic units on a discontinuous sucrose gradient. This preparation provides the first practical procedure for the isolation of postsynaptic densities, prominent organelles of unknown function, without the use of detergents, enabling retention of the postsynaptic membrane in association with the postsynaptic density. The preparation shows enhanced binding of spiroperidol, a dopamine agonist, which, in conjunction with morphological evidence, indicates that the preparation is sufficiently intact to enable study of the interaction of the postsynaptic membrane with the postsynaptic density. Actin, alpha- and beta-tubulin and postsynaptic density protein constitute the major proteins in the preparation; they are present in amounts of 41, 54, 57 and 74 micrograms per mg protein, respectively; as compared to 54, 59, 55 and 9 micrograms per mg protein of the synaptic junctional membrane used as starting material. The utility of the preparation for a number of localization studies, including ion translocating adenosine 5'-triphosphatases, protein kinases and their substrates is discussed.
Topics: Actins; Animals; Axons; Cell Fractionation; Cell Separation; Cerebral Cortex; Intermediate Filament Proteins; Neurofilament Proteins; Rats; Spiperone; Synapses; Synaptic Membranes; Tubulin
PubMed: 6413886
DOI: 10.1016/0306-4522(83)90179-3 -
Current Opinion in Insect Science Dec 2023Insects rely on their sense of smell to navigate complex environments and make decisions regarding food and reproduction. However, in natural settings, the odors that... (Review)
Review
Insects rely on their sense of smell to navigate complex environments and make decisions regarding food and reproduction. However, in natural settings, the odors that convey this information may come mixed with environmental odors that can obscure their perception. Therefore, recognizing the presence of informative odors involves generalization and discrimination processes, which can be facilitated when there is a high contrast between stimuli, or the internal representation of the odors of interest outcompetes that of concurrent ones. The first two layers of the olfactory system, which involve the detection of odorants by olfactory receptor neurons and their encoding by the first postsynaptic partners in the antennal lobe, are critical for achieving such optimal representation. In this review, we summarize evidence indicating that experience-dependent changes adjust these two levels of the olfactory system. These changes are discussed in the context of the advantages they provide for detection of informative odors.
Topics: Animals; Olfactory Pathways; Smell; Odorants; Olfactory Receptor Neurons
PubMed: 37741614
DOI: 10.1016/j.cois.2023.101117 -
Neuroscience Letters Mar 1979We have reported previously that at dendritic spine synapses, the spine apparatus is associated with the synaptic spinule. In this report this association is shown, in...
We have reported previously that at dendritic spine synapses, the spine apparatus is associated with the synaptic spinule. In this report this association is shown, in serial thin sections, to involve intimate physical proximity between the postsynaptic density and membranous structures that are part of, or extend from, the spine apparatus itself. Because of the variegated shapes of synaptic spinules, the spine apparatus-postsynaptic density relation suggests participation in membrane distribution or synaptic remodeling phenomena.
Topics: Animals; Dendrites; Hippocampus; Male; Microscopy, Electron; Rats; Synaptic Membranes
PubMed: 514542
DOI: 10.1016/0304-3940(79)90010-7 -
Lipid Membrane State Change by Catalytic Protonation and the Implications for Synaptic Transmission.Membranes Dec 2021In cholinergic synapses, the neurotransmitter acetylcholine (ACh) is rapidly hydrolyzed by esterases to choline and acetic acid (AH). It is believed that this reaction...
In cholinergic synapses, the neurotransmitter acetylcholine (ACh) is rapidly hydrolyzed by esterases to choline and acetic acid (AH). It is believed that this reaction serves the purpose of deactivating ACh once it has exerted its effect on a receptor protein (AChR). The protons liberated in this reaction, however, may by themselves excite the postsynaptic membrane. Herein, we investigated the response of cell membrane models made from phosphatidylcholine (PC), phosphatidylserine (PS) and phosphatidic acid (PA) to ACh in the presence and absence of acetylcholinesterase (AChE). Without a catalyst, there were no significant effects of ACh on the membrane state (lateral pressure change ≤0.5 mN/m). In contrast, strong responses were observed in membranes made from PS and PA when ACh was applied in presence of AChE (>5 mN/m). Control experiments demonstrated that this effect was due to the protonation of lipid headgroups, which is maximal at the pK (for PS: pKCOOH≈5.0; for PA: pKHPO4-≈8.5). These findings are physiologically relevant, because both of these lipids are present in postsynaptic membranes. Furthermore, we discussed evidence which suggests that AChR assembles a lipid-protein interface that is proton-sensitive in the vicinity of pH 7.5. Such a membrane could be excited by hydrolysis of micromolar amounts of ACh. Based on these results, we proposed that cholinergic transmission is due to postsynaptic membrane protonation. Our model will be falsified if cholinergic membranes do not respond to acidification.
PubMed: 35054529
DOI: 10.3390/membranes12010005