SEARCH · PubMed Health

Results for “synaptic vesicles”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 631 records · Page 35Linked to original sources

PubMed1995

Synaptic vesicle depletion in reticulospinal axons is reduced by 5-hydroxytryptamine: direct evidence for presynaptic modulation of glutamatergic transmission.

5-hydroxytryptamine (5-HT; serotonin) is known to depress glutamatergic synaptic transmission in the spinal cord of vertebrates. To test directly whether 5-HT inhibits synaptic glutamate release, we examined its effect on the ultrastructure of synaptic vesicle clusters in giant reticulospinal axons in a lower vertebrate (lamprey; Lampetra fluviatilis). The size of these axons makes it possible to selectively expose only a part of the presynaptic element to 5-HT, while another part of the same axon is maintained in control solution. Action potential stimulation at 20 Hz for 20 min caused a marked reduction in the number of synaptic vesicles in active zones maintained in control solution, while in the part exposed to 5-HT (20 microM) the number of synaptic vesicles per active zone was approximately 3-fold higher. In contrast, 5-HT had no effect on the number of vesicles in resting axons. To examine whether 5-HT acts by reducing presynaptic Ca2+ influx, intra-axonal recordings of Ba2+ potentials were performed. No reduction of the axonal Ba2+ potential could be detected after application of 20 or 200 microM 5-HT. The present results show that 5-HT reduces the rate of synaptic exocytosis in reticulospinal axons. The effect appears to be mediated by a mechanism distinct from the presynaptic Ca2+ channels.

Action Potentials↗

PubMed1989

Regulation of the vesamicol receptor in cholinergic synaptic vesicles by acetylcholine and an endogenous factor.

Cholinergic synaptic vesicles obtained from Torpedo electric organ have an active transport system for acetylcholine (ACh). Linked to ACh transport is a cytoplasmically oriented receptor for the inhibitory drug (-)-trans-2-(4-phenylpiperidino)cyclohexanol (vesamicol, formerly AH5183). Storage of freshly isolated vesicles for several days leads to more vesamicol binding. This can be induced immediately by hyposmotic lysis of the vesicles, which reseal to form right-side-out ghosts. The increased drug binding was due to a twofold increase in the affinity and a 20% increase in the amount of the receptor expressed, probably as a result of the release of an endogenous factor. Binding of vesamicol to ghosts was specifically inhibited by exogenous ACh acting with a dissociation constant of 18 mM. This suggests that the vesamicol binding site probably is linked to a low-affinity ACh binding site that is different from the higher affinity transport binding site. Equilibrium and kinetic attempts to determine whether exogenous ACh acts on the outside or the inside of the ghost membrane to inhibit vesamicol binding failed because of rapid equilibration of exogenous ACh across the ghost membrane. It is argued that the endogenous factor released by hyposmotic lysis might be ACh. Potential roles for such a transmembrane signal regulating the vesamicol receptor are discussed.

Acetylcholine↗

PubMed1978

Purification of synaptic vesicles from elasmobranch electric organ and the use of biophysical criteria to demonstrate purity.

We have purified cholinergic synaptic vesicles from the electric organs of two related marine elasmobranchs, Torpedo californica and Narcine brasiliensis, to a specific activity higher than had previously been obtained. We have demonstrated the homogeneity of the vesicles by biophysical criteria. The purification scheme consisted of differential centrifugation, flotation equilibrium in sucrose density gradients, and permeation chromatography on glass bead columns of average pore size 3000 A. Our criteria for purity were that bound acetylcholine, bound nucleotide triphosphate, protein, and lipid--phosphorus behave identically when vesicles were analyzed by procedures which depend on vesicle size, density, and charge. Contaminants were not detected when vesicles were fractionated by preparative and analytical sedimentation, by preparative equilibrium sedimentation using glycerol density gradients, or by electrophoresis in Ficoll density gradients. Pure synaptic vesicles, which have been purified 290-fold from the initial homogenate, contain per mg of protein: 8 mumol of acetylcholine, 3 mumol of ATP, and 7 mumol of lipid phosphorus. These procedures may be of general value in the purification of membrane vesicles.

Animals↗

PubMed2005

Acrylamide inhibits dopamine uptake in rat striatal synaptic vesicles.

Evidence suggests that acrylamide (ACR) neurotoxicity is mediated by decreased presynaptic neurotransmitter release. Defective release might involve disruption of neurotransmitter storage, and therefore, we determined the effects of in vivo and in vitro ACR exposure on 3H-dopamine (DA) transport into rat striatal synaptic vesicles. Results showed that vesicular DA uptake was decreased significantly in rats intoxicated at either 50 mg/kg/day x 5 days or 21 mg/kg/day x 21 days. ACR intoxication also was accompanied by a reduction in KCl-evoked synaptosomal DA release, although consistent changes in presynaptic membrane transport were not observed. Silver stain and immunoblot analyses suggested that reduced vesicular uptake was not due to active nerve terminal degeneration or to a reduction in the synaptic vesicle content of isolated striatal synaptosomes. Nor did the in vivo presynaptic effects of ACR involve changes in synaptosomal glutathione concentrations. In vitro exposure of striatal vesicles showed that both ACR and two sulfhydryl reagents, N-ethylmaleimide (NEM) and iodoacetic acid (IAA), produced concentration-dependent decreases in 3H-DA uptake. Although ACR was significantly less potent than either NEM or IAA, all three chemicals caused comparable maximal inhibitions of vesicular uptake. Kinetic analysis of DA uptake showed that in vitro exposure to either ACR or NEM decreased V(max) and increased K(m). Determination of radiolabel efflux from 3H-DA-loaded vesicles indicated that in vitro ACR did not affect neurotransmitter retention. These data suggest that ACR impaired neurotransmitter uptake into striatal synaptic vesicles, possibly by interacting with sulfhydryl groups on functionally relevant proteins. The resulting disruption of neurotransmitter storage might mediate defective presynaptic release.

Acrylamide↗

PubMed2001

synaptotagmin mutants reveal essential functions for the C2B domain in Ca2+-triggered fusion and recycling of synaptic vesicles in vivo.

Synaptotagmin has been proposed to function as a Ca(2+) sensor that regulates synaptic vesicle exocytosis, whereas the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex is thought to form the core of a conserved membrane fusion machine. Little is known concerning the functional relationships between synaptotagmin and SNAREs. Here we report that synaptotagmin can facilitate SNARE complex formation in vitro and that synaptotagmin mutations disrupt SNARE complex formation in vivo. Synaptotagmin oligomers efficiently bind SNARE complexes, whereas Ca(2+) acting via synaptotagmin triggers cross-linking of SNARE complexes into dimers. Mutations in Drosophila that delete the C2B domain of synaptotagmin disrupt clathrin AP-2 binding and endocytosis. In contrast, a mutation that blocks Ca(2+)-triggered conformational changes in C2B and diminishes Ca(2+)-triggered synaptotagmin oligomerization results in a postdocking defect in neurotransmitter release and a decrease in SNARE assembly in vivo. These data suggest that Ca(2+)-driven oligomerization via the C2B domain of synaptotagmin may trigger synaptic vesicle fusion via the assembly and clustering of SNARE complexes.

Adaptor Protein Complex alpha Subunits↗

PubMed1999

The mammalian brain high-affinity L-proline transporter is enriched preferentially in synaptic vesicles in a subpopulation of excitatory nerve terminals in rat forebrain.

The expression of a brain-specific high-affinity Na+-dependent (and Cl--dependent) L-proline transporter (PROT) in subpopulations of putative glutamatergic neurons in mammalian brain suggests a physiological role for this carrier in excitatory neurotransmission (). To gain insights into potential sites where PROT may function, we used a C-terminal domain antipeptide antibody to determine the regional distribution and subcellular localization of PROT in rat forebrain. PROT immunoreactivity was seen in processes having a regional light microscopic distribution comparable to that of known glutamatergic projections within the cortex, caudate putamen nucleus (CPN), hippocampal formation, and other forebrain regions. In all regions examined by electron microscopy (cortex, CPN, and the stratum oriens of CA1), PROT labeling was observed primarily within subpopulations of axon terminals forming asymmetric excitatory-type synapses. Immunogold labeling for PROT was detected in close contact with membranes of small synaptic vesicles (SSVs) and more rarely with the plasma membrane in these axon terminals. Subcellular fractionation studies confirmed the preferential distribution of PROT to synaptic vesicles. The topology of PROT in synaptic vesicles was found to be inverted with respect to the plasma membrane, suggesting that PROT-containing vesicles are generated by a process involving endocytosis from the plasma membrane. Because PROT lacks any of the known characteristics of other vesicular transporters, these results suggest that certain excitatory terminals have a reserve pool of PROT associated with SSVs. The delivery of PROT to the plasma membrane by exocytosis could play a critical role in the plasticity of certain glutamatergic pathways.

Amino Acid Sequence↗

PubMed2002

Impairment of synaptic vesicle exocytosis and recycling during neuromuscular weakness produced in mice by 2,4-dithiobiuret.

Chronic treatment of rodents with 2,4-dithiobiuret (DTB) induces a neuromuscular syndrome of flaccid muscle weakness that mimics signs seen in several human neuromuscular disorders such as congenital myasthenic syndromes, botulism, and neuroaxonal dystrophy. DTB-induced muscle weakness results from a reduction of acetylcholine (ACh) release by mechanisms that are not yet clear. The objective of this study was to determine if altered release of ACh during DTB-induced muscle weakness was due to impairments of synaptic vesicle exocytosis, endocytosis, or internal vesicular processing. We examined motor nerve terminals in the triangularis sterni muscles of DTB-treated mice at the onset of muscle weakness. Uptake of FM1-43, a fluorescent marker for endocytosis, was reduced to approximately 60% of normal after either high-frequency nerve stimulation or K(+) depolarization. Terminals ranged from those with nearly normal fluorescence ("bright terminals") to terminals that were poorly labeled ("dim terminals"). Ultrastructurally, the number of synaptic vesicles that were labeled with horseradish peroxidase (HRP) was also reduced by DTB to approximately 60%; labeling among terminals was similarly variable. A subset of DTB-treated terminals having abnormal tubulovesicular profiles in their centers did not respond to stimulation with increased uptake of HRP and may correspond to dim terminals. Two findings suggest that posttetanic "slow endocytosis" remained qualitatively normal: the rate of this type of endocytosis as measured with FM1-43 did not differ from normal, and HRP was observed in organelles associated with this pathway- coated vesicles, cisternae, as well as synaptic vesicles but not in the tubulovesicular profiles. In DTB-treated bright terminals, end-plate potential (EPP) amplitudes were decreased, and synaptic depression in response to 15-Hz stimulation was increased compared with those of untreated mice; in dim terminals, EPPs were not observed during block with D-tubocurarine. Nerve-stimulation-induced unloading of FM1-43 was slower and less complete than normal in bright terminals, did not occur in dim terminals, and was not enhanced by alpha-latrotoxin. Collectively, these results indicate that the size of the recycling vesicle pool is reduced in nerve terminals during DTB-induced muscle weakness. The mechanisms by which this reduction occurs are not certain, but accumulated evidence suggests that they may include defects in either or both exocytosis and internal vesicular processing.

Animals↗

PubMed1975

Influence of castration on incorporation of exogenous peroxidase into "synaptic" vesicles of the median eminence. II. The perivascular part of the palisade zone in male rats.

In the median eminence of male rats, nerve profiles in the immediate vicinity of portal capillaries have been divided into 4 categories on the basis of their vesicular content: profiles a with agranular "synaptic" vesicles of about 50 nm, b with similar agranular vesicles and also with granular vesicles of mainly 60-140 nm, c with granular vesicles alone and d without vesicles. Twenty-four hours after castration, the percentage of profiles of category a was significantly increased when compared with sham-operated animals, whereas the percentage of profiles of category b was significantly decreased. After intravenous injection of exogenous peroxidase, especially the nerve profiles located in direct contact with the outer basement membrane of the portal capillaries contained peroxidase positive "synaptic" vesicles. Injection off peroxidase after castration resulted in a significant increase in the percentage of nerve profiles containing both peroxidase positive and peroxidase negative "synaptic" vesicles (category a). It is suggested that, in certain nerve terminals, castration may lead to release off the content of granular vesicles, which may contain gonadotropin releasing factor. This release then may cause that nerve terminals with agranular vesicles and granular vesicles (category b) change in their vesicular content and are therefore classified as terminals with only agranular vesicles (category a). An increased turnover rate in the ultrastructurally affected terminals may be reflected in increased uptake of exogenous peroxidase. The observations imply that certain neurones projecting to portal capillaries in the median eminence are, directly or indirectly, sensitive to changes in the level of gonadal steroids.

Animals↗

PubMed1987

Axonal transport of the synaptic vesicle monoamine carrier identified by [3H]dihydrotetrabenazine binding in rat sciatic nerve.

The monoamine carrier of noradrenergic synaptic vesicles was assayed in the rat sciatic nerve by in vitro binding of [3H]dihydrotetrabenazine. The number of binding sites increased with time on both sides of a ligature, indicating fast anterograde and retrograde axoplasmic transports of comparable amplitude. Anterogradely and retrogradely transported binding sites had similar pharmacological properties, which were characteristic of binding to the monoamine carrier embedded within a lipid bilayer. Contrary to the secreted synaptic vesicle matrix constituents, the intrinsic monoamine carrier assayed by [3H]dihydrotetrabenazine binding is a marker adapted to retrograde transport studies.

Animals↗

PubMed2006

Rustling synaptic vesicle cargo after exocytosis.

In this issue of Neuron, Voglmaier et al. provide new evidence that the retrieval of synaptic vesicle transporters after exocytosis proceeds along at least two different endocytic pathways. This work provides new insight into the mechanisms of sorting synaptic vesicle cargo at the cell surface.

Acyltransferases↗

PubMed1986

Identification of a synaptic vesicle antigen (Mr 86,000) conserved between Torpedo and rat.

Antisera were raised in guinea pigs to synaptic vesicles purified from the electric organ of Torpedo marmorata. In cholinergic nerve terminals from Torpedo the major antigens identified had Mr 300,000-150,000, 86,000, and 18,000. The Mr 86,000 antigen was conserved between Torpedo and rat, where it is neuron-specific and concentrated in nerve terminals. When rat brain synaptosomes are subfractionated the antigen is associated with synaptic vesicles. The antigen is not found in the cytoskeleton and in the vesicle-free cytosol. Immunohistochemical localization of the antigen in rat shows it to be associated with synapses in diaphragm, cerebellum, hippocampus, and cerebral cortex. The staining pattern of the antigen indicates that the antigen is not cholinergic-specific. The function of the Mr 86,000 antigen remains to be identified.

Animals↗

PubMedDate not supplied

[Effect of NAD on uptake and release of some mediators by synaptic vesicles of the rat's brain].

NAD has been studied for its effect on the uptake of serotonin, norepinephrine, dopamine and GABA by synaptic vesicles. It has been shown that norepinephrine and dopamine uptake is not altered by addition of 10(-3) M, 10(-6) M, 10(-8) M, 10(-9) M and 10(-12) M NAD concentrations to incubation medium while the serotonin uptake is increased by 29, 47, 23, 24 and 18%, respectively. 10(-3) M and 10(-6) M NAD concentrations decrease GABA uptake by 30% and 24%. The study of 10(-6) M NAD effect on serotonin release from serotonin pre-loaded vesicles demonstrated the marked elevation of the neurotransmitter release, especially during the first 4 minutes of incubation (by 40%). The similar effect on serotonin release, is observed after addition of KCl, standard depolarizing agent, to the incubation medium. In contrast to synaptic membranes, the red blood cell membranes did not activate the neurotransmitter release after addition of serotonin pre-loaded vesicles to incubation medium, which proves the specificity of synaptic vesicles--synaptic membranes interaction. The modulating NAD action at the presynaptic membrane level can also be assumed.

Animals↗

PubMed1997

Mints, Munc18-interacting proteins in synaptic vesicle exocytosis.

Munc18-1 is a neuronal protein that interacts with syntaxin 1 and is required for synaptic vesicle exocytosis. We have now identified two Munc18-1-interacting proteins called Mint1 and Mint2 that may mediate the function of Munc18-1. Mint proteins are detectable only in brain and are composed of an N-terminal sequence that binds Munc18-1, a middle phosphotyrosine-binding domain, and two C-terminal PDZ domains thought to attach proteins to the plasma membrane. In brain, Mint proteins are part of a multimeric complex containing Munc18-1 and syntaxin that likely functions as an intermediate in synaptic vesicle docking/fusion. The phosphotyrosine-binding domain specifically binds to phosphatidylinositol phosphates known to be produced during vesicle exocytosis (Hay, J. C., Fisette, P. L., Jenkins, G. H., Fukami, K., Takonawa, T., Anderson, R. A., and Martin, T. F. J. (1995) Nature 374, 173-177). Our data suggest a model whereby local production of phosphatidylinositol phosphates may trigger the binding of vesicles to the active zone via the Mint.Munc18-1 complex in conjunction with syntaxin 1.

Adaptor Proteins, Signal Transducing↗

PubMed1993

The synaptic vesicle protein synaptotagmin promotes formation of filopodia in fibroblasts.

Neuronal filopodia are actin-rich cytoplasmic extensions that are involved in motility and recognition in growth cones and maturing axonal endings. A detailed understanding of neuronal growth will depend on clarification of the membrane fusion events occurring during filopodial extension. The synaptic vesicle protein synaptotagmin seems to be intimately involved in exocytotic membrane fusion. Here we show that fibroblast cell lines transfected with synaptotagmin form long, highly branched, actin-rich filopodial processes, with the expressed synaptotagmin being incorporated into the plasma membrane. In contrast, cell lines expressing either of two other synaptic vesicle proteins, SV2 or synaptophysin, generate only rudimentary processes, and, like neurons, sort SV2 and synaptophysin to small intracellular vesicles. As presynaptic calcium entry regulates synaptic vesicle fusion, our results indicate that synaptotagmin might link neuronal activity with synaptic growth.

Animals↗

PubMed1987

Effect of collidine (2,4,6-trimethylpyridine) on the osmiophilia and chromaffin reaction in the synaptic vesicles of rat pineal nerves.

Rat pineal nerve endings contain a population of small and of large synaptic vesicles that are either electron lucent or have electron-dense cores. It has been reported that their osmiophilia is eliminated when collidine buffer is used in the fixation procedure. We investigated this effect and found that osmium tetroxide and potassium dichromate reactivity were abolished when excised pineal glands were briefly incubated with collidine buffer before glutaraldehyde-cacodylate fixation. Such an effect was not observed when collidine was applied after fixation. Glands that had been fixed in glutaraldehyde or osmium tetroxide buffered with collidine exhibited a peripheral zone containing reactive synaptic vesicles and a deeper, central zone where such reactivity was absent. These results indicate that the effect of collidine is due to depletion of monoamines rather than to chemical blockage of their reactivity, and further suggest that collidine has a higher rate of penetration into tissues than the tested fixatives.

Animals↗

PubMed2001

Morphological correlates of functionally defined synaptic vesicle populations.

By combining photoconversion of FM1-43-stained vesicles and electron microscopy of hippocampal synapses, we find evidence that the population of morphologically docked synaptic vesicles corresponds to the release-ready neurotransmitter quanta. Furthermore, those synaptic vesicles that are participating in cycles of exo- and endocytosis tend to be closer to the active zone than vesicles that are being held in reserve.

Animals↗

PubMed1998

Mannose-specific recognition mediates two aspects of synaptic growth of leech sensory afferents: collateral branching and proliferation of synaptic vesicle clusters.

The developmental role of carbohydrate markers in the genesis of neuronal networks was studied using leech sensory afferents as a model. Leech sensory afferents express a mannose-containing epitope on their cell surface that is recognized by monoclonal antibody Lan3-2. Previously, the elaboration of sensory arbors in the synaptic neuropil of CNS ganglia was experimentally shown to depend on this mannose marker. Sensory arbors were abolished by perturbing sensory afferents in the intact nervous system with Lan3-2 Fab fragments, a glycosidase, or mannose-BSA. To understand the cytological mechanisms underlying mannose-specific recognition for synaptogenesis, we have now studied the effects of antibody perturbation at the ultrastructural level in the sensory afferent target region. A characteristic signature of a normal sensory afferent is its profuse collateral branching, which, with ongoing development, is replaced by a single widened process, the sensory trunk, which possesses numerous synaptic vesicle clusters. The inhibition of mannose-specific recognition leads to a rapid, major reorganization of different stages of sensory afferent growth. Collateral branches at the distal growing region are reduced three- to fourfold. The pruned axons grow at an accelerated rate. Developmentally older sensory trunks experience a threefold reduction in synaptic vesicle clusters. These responses suggest that depriving sensory afferents of mannose-specific recognition aborts their synaptogenesis and causes them to resume behavior typical of tracking through axonal tracts. The current findings also suggest that the mannose marker, by promoting both collateral branching andthe proliferation of synaptic vesicle clusters, plays a critical role in two stages of sensory afferent synaptogenesis.

Animals↗

PubMed2005

Zn7metallothionein-3 and the synaptic vesicle cycle: interaction of metallothionein-3 with the small GTPase Rab3A.

In the central nervous system, a large amount of chelatable Zn(2+) is sequestered in presynaptic vesicles of certain glutamatergic nerve terminals. The exo-endocytotic cycle of synaptic vesicles is strictly linked to the small GTPase Rab3A. Metallothionein-3 (Zn(7)MT-3) has been proposed to be involved in the intracellular trafficking of Zn(2+) in zinc-containing neurons, but its role in this process is not understood. By using affinity precipitation and surface plasmon resonance analysis, we show that Zn(7)MT-3 binds reversibly to Rab3A.GDP (K(D) = 2.6 microM), but not to Rab3A.GTP. The binding of Zn(7)MT-3 to Rab3A.GDP is specific as no binding was observed with the metal-free form of MT-3. Mutational studies of Rab3A mapped the interaction site to the effector binding site of the protein. This location is further supported by the kinetics of GDP exchange, which was found to be unaffected by binding of Zn(7)MT-3 to Rab3A.GDP. The interaction of Zn(7)MT-3 with Rab3A indicates that Zn(7)MT-3 is not merely a cellular Zn(2+) buffer, but actively participates in synaptic vesicle trafficking upstream of vesicle fusion.

Chemical Precipitation↗