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Results for “synaptic vesicles”

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PubMed1989

Alignment and intracytoplasmic disintegration of synaptic vesicles in the brain cortex.

Perfusion fixation with highly concentrated aldehydes suggests that the synaptic vesicles undergo disintegration within the presynaptic ending upon touching the presynaptic membrane rather than being released by exocytosis into the intersynaptic cleft. Three factors have been explored in order to inquire further into the possible significance of the findings: (a) fixative concentration; (b) physiological activity; (c) cell depolarization. The transformation of the vesicles into amorphous, electron-dense material was observed in all experiments in all synapses, including those fixed with the lowest concentration of aldehydes. Besides, after acute ischemia and perfusion of excitatory and depolarizing pharmacological agents, the synaptic vesicles were seen to conflue upon the intersynaptic cleft in well-aligned rows. It was also found that the vesicles flow post mortem towards the intersynaptic cleft with absolute specificity.

Aldehydes↗

PubMed1997

Biochemical evidence for the presence of NAP-22, a novel acidic calmodulin binding protein, in the synaptic vesicles of rat brain.

NAP-22 is a neuronal tissue-enriched acidic protein which is expressed predominantly in rat brain. In the present study, we quantitated the amount of NAP-22 in a highly purified synaptic vesicle fraction. NAP-22 comprised 1.3 +/- 0.15% of the total protein in the fraction, and NAP-22 was located on the external surface of the synaptic vesicle membrane. The results suggest NAP-22 may be involved in the synaptic vesicle cycling.

Animals↗

PubMed1988

Differential effect of alpha-latrotoxin on exocytosis from small synaptic vesicles and from large dense-core vesicles containing calcitonin gene-related peptide at the frog neuromuscular junction.

The regulatory peptide called calcitonin gene-related peptide (CGRP) was detected by immunofluorescence in frog motor neurons and motor nerve terminals. In motor nerve terminals, CGRP-like immunoreactivity was found to be segregated within large dense-core vesicles. To determine whether exocytosis from acetylcholine-containing small synaptic vesicles and from CGRP-containing large dense-core vesicles can be independently stimulated, nerve-muscle preparations were exposed to alpha-latrotoxin. This toxin induced complete depletion of acetylcholine-containing small synaptic vesicles but did not induce a parallel depletion of CGRP-like immunoreactivity and of large dense-core vesicles. These effects were independent of the presence of extracellular Ca2+ and occurred both at room temperature and at low temperature (1-3 degrees C). These findings suggest that exocytosis from the two vesicle populations is mediated by distinct biochemical mechanisms, which might be differentially regulated by physiological stimuli.

Animals↗

PubMed2006

Rab3 superprimes synaptic vesicles for release: implications for short-term synaptic plasticity.

Presynaptic vesicle trafficking and priming are important steps in regulating synaptic transmission and plasticity. The four closely related small GTP-binding proteins Rab3A, Rab3B, Rab3C, and Rab3D are believed to be important for these steps. In mice, the complete absence of all Rab3s leads to perinatal lethality accompanied by a 30% reduction of probability of Ca2+-triggered synaptic release. This study examines the role of Rab3 during Ca2+-triggered release in more detail and identifies its impact on short-term plasticity. Using patch-clamp electrophysiology of autaptic neuronal cultures from Rab3-deficient mouse hippocampus, we show that excitatory Rab3-deficient neurons display unique time- and frequency-dependent short-term plasticity characteristics in response to spike trains. Analysis of vesicle release and repriming kinetics as well as Ca2+ sensitivity of release indicate that Rab3 acts on a subset of primed, fusion competent vesicles. They lower the amount of Ca2+ required for action potential-triggered release, which leads to a boosting of release probability, but their action also introduces a significant delay in the supply of these modified vesicles. As a result, Rab3-induced modifications to primed vesicles causes a transient increase in the transduction efficacy of synaptic action potential trains and optimizes the encoding of synaptic information at an intermediate spike frequency range.

Animals↗

PubMed2005

The v-ATPase V0 subunit a1 is required for a late step in synaptic vesicle exocytosis in Drosophila.

The V(0) complex forms the proteolipid pore of an ATPase that acidifies vesicles. In addition, an independent function in membrane fusion has been proposed largely based on yeast vacuolar fusion experiments. We have isolated mutations in the largest V(0) component vha100-1 in flies in an unbiased genetic screen for synaptic malfunction. The protein is only required in neurons, colocalizes with markers for synaptic vesicles as well as active zones, and interacts with t-SNAREs. Loss of vha100-1 leads to vesicle accumulation in synaptic terminals, suggesting a deficit in release. The amplitude of spontaneous release events and release with hypertonic stimulation indicate normal levels of neurotransmitter loading, yet mutant embryos display severe defects in evoked synaptic transmission and FM1-43 uptake. Our data suggest that Vha100-1 functions downstream of SNAREs in synaptic vesicle fusion.

Animals↗

PubMed1985

The localization and rate of disappearance of a synaptic vesicle antigen following denervation.

A proteoglycan-specific antiserum has been used to monitor the effects of denervation in the electric organ of Torpedo marmorata. The antiserum was produced by injecting a highly purified synaptic vesicle fraction prepared from the electric organs of Torpedo marmorata. Following absorption the serum appears to be specific towards synaptic vesicles. The ultrastructural localization of the antigen determined by immuno-electron microscopy confirmed the specificity of the antiserum and showed that it did not cross-react with the proteoglycans of the basal lamina. The rate of disappearance of the vesicle proteoglycans following denervation was evaluated by means of the antiserum and was compared to the rate of disappearance of other vesicular and nerve terminal-associated markers. The results suggest that degeneration affects the vesicular constituents at varying rates resulting in a progressive disappearance of the entire functional capacity of the synaptic vesicles.

Acetylcholine↗

PubMed2000

Distinct requirements for the AP-3 adaptor complex in pigment granule and synaptic vesicle biogenesis in Drosophila melanogaster.

The AP-3 adaptor protein complex has been implicated in the biogenesis of lysosome-related organelles, such as pigment granules/melanosomes, and synaptic vesicles. Here we compare the relative importance of AP-3 in the biogenesis of these organelles in Drosophila melanogaster. We report that the Drosophila pigmentation mutants orange and ruby carry genetic lesions in the sigma3 and beta3-adaptin subunits of the AP-3 complex, respectively. Electron microscopy reveals dramatic reductions in the numbers of electron-dense pigment granules in the eyes of these AP-3 mutants. Mutant flies also display greatly reduced levels of pigments housed in these granules. In contrast, electron microscopy of retinula cells reveals numerous synaptic vesicles in both AP-3 mutant and wild-type flies, while behavioral assays show apparently normal locomotor ability of AP-3 mutant larvae. Together, these results demonstrate that Drosophila AP-3 is critical for the biogenesis of pigment granules, but is apparently not essential for formation of a major population of synaptic vesicles in vivo.

Adaptor Protein Complex alpha Subunits↗

PubMed1975

[Effect of carbidine on the content and storage of adrenergic neurotransmitter in the synaptic vesicles].

The influence of carbidine, an original psychotropic drug, on the adrenergic neurotransmitter content and storage in the sympathetic nerves was studied with the use of cytochemical electron microscopy. The influence of carbidine on the uptake of the exogenous noradrenaline (NA) in the synaptic vesicles was also studied. Carbidine was found to be capable to decreasing the NA storage in the synaptic vesicles and failed to block the accumulation of the exogenous NA in the synaptic vesicles.

Amines↗

PubMed2004

The lipid binding pleckstrin homology domain in UNC-104 kinesin is necessary for synaptic vesicle transport in Caenorhabditis elegans.

UNC-104 (KIF1A) is a kinesin motor that transports synaptic vesicles from the neuronal cell body to the terminal. Previous in vitro studies have shown that a Dictyostelium relative of UNC-104 transports liposomes containing acidic phospholipids, but whether this interaction is needed for the recognition and transport of synaptic vesicles in metazoans remains unexplored. Here, we have introduced mutations in the nonmotor domain of UNC-104 and examined whether these mutant motors can rescue an unc-104 Caenorhabditis elegans strain. We show that a pleckstrin homology (PH) domain in UNC-104 is essential for membrane transport in living C. elegans, that this PH domain binds specifically to phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)), and that point mutants in the PH domain that interfere with PI(4,5)P(2) binding in vitro also interfere with UNC-104 function in vivo. Several other lipid-binding modules could not effectively substitute for the UNC-104 PH domain in this in vivo assay. Real time imaging also revealed that a lipid-binding point mutation in the PH domain reduced movement velocity and processivity of individual UNC-104::GFP punctae in neurites. These results reveal a critical role for PI(4,5)P(2) binding in UNC-104-mediated axonal transport and shows that the cargo-binding properties of the distal PH domain can affect motor output.

Amino Acid Sequence↗

PubMed2006

Actin polymerization regulates clathrin coat maturation during early stages of synaptic vesicle recycling at lamprey synapses.

Although it is established that presynaptic actin participates in synaptic vesicle recycling at several synapses, the earliest stages at which actin polymerization is employed during this process are still unclear. To address this, we prevented actin polymerization at lamprey synapses by applying latrunculin B or swinholide A. Latrunculin and swinholide depolymerize actin by sequestering actin monomers and, in addition, swinholide can sever existing actin filaments. When injected into individual presynaptic axons of the intact spinal cord, fluorescently labeled monomeric actin rapidly incorporated in a calcium-dependent manner into a stable, filamentous actin network concentrated at endocytic zones. This pool of actin was disrupted completely by latrunculin. At stimulated synapses, specific disruption of actin polymerization with latrunculin and swinholide induced a selective increase in unconstricted clathrin-coated pits and, in the case of swinholide, an additional increase in the size of plasma membrane evaginations. These results indicate that actin polymerization participates initially in the maturation of clathrin-coated pits during early stages of synaptic vesicle recycling.

Actin Cytoskeleton↗

PubMed1996

Distribution of Rab3a in rat nervous system: comparison with other synaptic vesicle proteins and neuropeptides.

In the present study we have investigated the distribution of Rab3a in rat peripheral nervous system and compared it with the distribution of other synaptic vesicle proteins (synaptophysin, synapsin I), neuropeptides (CGRP, SP, NPY) and tyrosine hydroxylase (TH). Rab3a immunoreactivity (-IR) was always colocalized with synaptophysin-IR and synapsin I-IR in nerve terminals of the spinal cord and peripheral nerve endings. In many cases, Rab3a-IR was also present in the same axons and terminals as peptides. In crushed sciatic nerve axons, Rab3a was colocalized, proximal to the crush, with synaptophysin-IR, synapsin I-IR, CGRP-IR, and TH-IR, but only partially co-localized with NPY-IR and SP-IR. In the area distal to the crush, Rab3a-IR was very weakly positive in a few thin axons, while larger amount of synaptophysin, CGRP, NPY and SP immunoreactivities were detected. The subcellular distribution of peptides and Rab3a differed in that peptides were observed mainly in large granular structures, while Rab3a-IR was observed mainly as diffuse, finely granular immunoreactivity, in addition to a few exceptional large granules present in some axons. The results demonstrate that Rab3a is widely distributed in different types of neurons, i.e. motor, sensory, autonomic adrenergic and cholinergic neurons, and colocalized with other synaptic vesicle proteins, suggesting that Rab3a may play an essential role in neuronal function. Furthermore, Rab3a is present in many peptide containing axons and terminals, but with an apparently different subcellular distribution, being affiliated mostly with small synaptic vesicles and only occasionally with large vesicles, that may represent peptide contained vesicles.

Animals↗

PubMed2000

Stable SNARE complex prior to evoked synaptic vesicle fusion revealed by fluorescence resonance energy transfer.

Although it is clear that soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE) complex plays an essential role in synaptic vesicle fusion, the dynamics of SNARE assembly during vesicle fusion remain to be determined. In this report, we employ fluorescence resonance energy transfer technique to study the formation of SNARE complexes. Donor/acceptor pair variants of green fluorescent protein (GFP), cyan fluorescent protein (CFP), and yellow fluorescent protein (YFP) are fused with the N termini of SNAP-25 and synaptobrevin, respectively. In vitro assembly of SNARE core complex in the presence of syntaxin shows strong fluorescence resonance energy transfer (FRET) between the CFP-SNAP-25 and YFP-synaptobrevin. Under the same conditions, CFP fused to the C terminus of SNAP-25, and YFP- synaptobrevin have no FRET. Adenovirus-mediated gene transfer is used to express the fusion proteins in PC12 cells and cultured rat cerebellar granule cells. Strong FRET is associated with neurite membranes and vesicular structures in PC12 cells co-expressing CFP-SNAP-25 and YFP-synaptobrevin. In cultured rat cerebellar granule cells, FRET between CFP-SNAP-25 and YFP-synaptobrevin is mostly associated with sites presumed to be synaptic junctions. Neurosecretion in PC12 cells initiated by KCl depolarization leads to an increase in the extent of FRET. These results demonstrate that significant amounts of stable SNARE complex exist prior to evoked synaptic vesicle fusion and that the assembly of SNARE complex occurs during vesicle docking/priming stage. Moreover, it demonstrates that FRET can be used as an effective tool for investigating dynamic SNARE interactions during synaptic vesicle fusion.

Animals↗

PubMed2000

Expression of synaptic vesicle trafficking proteins in the developing rat pineal gland.

Adult mammalian pinealocytes contain several synaptic membrane proteins that are probably involved in the regulation of targeting and exocytosis of synaptic-like microvesicles (SLMVs). Immunohistochemical techniques have now demonstrated the spatiotemporal expression pattern of some of these proteins during rat pineal ontogenesis. Various synaptic vesicle trafficking proteins are detectable in proliferating epithelial cells of the pineal anlage even at embryonic day 17.5 (E 17.5), with the exception of syntaxin I (weakly expressed from E 19.5) and dynamin I (whose levels increase markedly during the first postnatal week). Numerous cells exhibiting strong immunoreactivity for synaptobrevin II, SNAP-25, synaptophysin, and munc-18-1 are distributed throughout the increasingly compact gland at E 19.5 and E 20.5; however, their number declines toward the proximal deep part of the organ. Groups of postmitotic cells situated at the surface of the developing gland exhibit marked immunoreactivity for the aforementioned proteins and lie close to the laminin-immunoreactive outer limiting basement membrane or to its remnants in regions of basement membrane dissolution. We also show that synthesis of vimentin and S-antigen seems to begin earlier during pineal development than previously recognized. Thus, synaptic vesicle trafficking proteins are the earliest molecular markers of pinealocyte differentiation known to date, being expressed well before the onset of rhythmic hormone secretion in the pineal gland, where they may play a role in morphogenetic events. Components of the extracellular matrix such as laminin may be critically involved in the upregulation of synaptic membrane protein expression. The dynamin immunostaining pattern indicates that SLMVs of pinealocytes begin to undergo regulated cycles of exo/endocytosis during postnatal week 1.

Animals↗

PubMed1976

Characterization of ATPases of plain synaptic vesicle and coated vesicle fractions isolated from rat brains.

The plain synaptic vesicle and the ocated vesicle fractions were isolated from rat brains, and the ATPase [EC 3.6.1.3] activities were characterized in terms of ionic effects, drug effects, and protein components. Coated vesicle fraction contained three times as much actomysin-like proteins as plain vesicle fraction, although both fractions had an identical ratio of actin-like protein to myosin-like protein. The ATPases of these two fractions were activated by both Mg2+ and Ca2+, and, in the presence of either of the cations, were inhibited by KCl. Reserpine activated plain vesicle ATPase only in the presence of Cl-. Colchicine and vinblastine inhibited coated vesicle ATPase only. The results are consistent with the view that actomyosin-like proteins are involved in the synaptic retrieval process.

Actins↗

PubMed2004

Identification of two cDNAs encoding synaptic vesicle protein 2 (SV2)-like proteins from epithelial tissues in the cat flea, Ctenocephalides felis.

Two distinct cDNAs that appear to encode proteins in the synaptic vesicle-2 (SV2) family were identified as expressed sequence tags from a Ctenocephalides felis hindgut and Malpighian tubule (HMT) cDNA library. To date, SV2 proteins have been described only in vertebrates, and have been detected only in synaptic vesicles in neuronal and endocrine tissues, where they are thought to regulate synaptic vesicle exocytosis. The cDNAs for the C. felis SV2-like proteins SVLP-1 and SVLP-2 encode predicted full-length proteins of 530 and 726 amino acids, respectively. Of characterized proteins, the SVLP protein sequences were most similar to rat SV2B. Northern blot analysis revealed that both mRNAs were up-regulated in larval stages that feed and in adults after feeding, and were expressed primarily or exclusively in the HMT tissues in adult fleas. These results suggest that the flea SVLP-1 and SVLP-2 gene products may have roles that are specific for the HMT tissues, and may differ in function from vertebrate SV2 proteins.

Amino Acid Sequence↗

PubMed1998

A tripartite protein complex with the potential to couple synaptic vesicle exocytosis to cell adhesion in brain.

We identify a complex of three proteins in brain that has the potential to couple synaptic vesicle exocytosis to neuronal cell adhesion. The three proteins are: (1) CASK, a protein related to MAGUKs (membrane-associated guanylate kinases); (2) Mint1, a putative vesicular trafficking protein; and (3) Veli1, -2, and -3, vertebrate homologs of C. elegans LIN-7. CASK, Mint1, and Velis form a tight, salt-resistant complex that can be readily isolated. CASK, Mint1, and Velis contain PDZ domains in addition to other modules. However, no PDZ domains are involved in complex formation, leaving them free to recruit cell adhesion molecules, receptors, and channels to the complex. We propose that the tripartite complex acts as a nucleation site for the assembly of proteins involved in synaptic vesicle exocytosis and synaptic junctions.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Differential expression between synaptic vesicle proteins and presynaptic plasma membrane proteins in the anterior horn of amyotrophic lateral sclerosis.

This study concerns the immunohistochemical investigation of synaptic proteins in the anterior horn of amyotrophic lateral sclerosis (ALS). Antibodies against synapsin 1 and synaptophysin (i.e. synaptic vesicle proteins), and those against syntaxin and the synaptosomal-associated, 25 kDa protein, SNAP25 (i.e. presynaptic plasma membrane proteins) were used for immunostaining, respectively. Lumbar spinal cords from five ALS and eight control patients were examined. In the controls, all four synaptic proteins exhibited fine granular immunoreactivities, distributed throughout the spinal gray matter almost uniformly. In contrast, in all five ALS patients, two of the synaptic vesicle proteins examined decreased in the anterior horn neuropil diffusely, while in the same lumbar segments of these cases the immunoreactivities of the two presynaptic plasma membrane proteins showed no apparent decrease, or were only mildly diminished in the same gray matter area. These results indicate that, during the presynaptic terminal degeneration in the anterior horn of ALS, synaptic vesicle involvement may precede that of the presynaptic plasma membrane.

Adult↗

PubMed1978

The effect of pentobarbital, chloralhydrate, ether and protoveratrine on the distribution of synaptic vesicles in rat cortical synaptosomes.

Rat cortical synaptosomes were incubated in a saline medium. On the addition of pentobarbital, chloralhydrate, ether and protoveratrine a redistribution of synaptic vesicles was revealed by electron microscopy. The anaesthetics decreased the number of synaptic vesicles attached to the presynaptic membrane while protoveratrine increased them. It is assumed that these agents affect the mechanism of vesicle reformation from the synaptosomal membrane and/or vesicle migration towards the synaptic cleft.

Animals↗