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Neuroscience Jan 1995Synaptic vesicles play the central role in synaptic transmission. They are regarded as key organelles involved in synaptic functions such as uptake, storage and... (Review)
Review
Synaptic vesicles play the central role in synaptic transmission. They are regarded as key organelles involved in synaptic functions such as uptake, storage and stimulus-dependent release of neurotransmitter. In the last few years our knowledge concerning the molecular components involved in the functioning of synaptic vesicles has grown impressively. Combined biochemical and molecular genetic approaches characterize many constituents of synaptic vesicles in molecular detail and contribute to an elaborate understanding of the organelle responsible for fast neuronal signalling. By studying synaptic vesicles from the electric organ of electric rays and from the mammalian cerebral cortex several proteins have been characterized as functional carriers of vesicle function, including proteins involved in the molecular cascade of exocytosis. The synaptic vesicle specific proteins, their presumptive function and targets of synaptic vesicle proteins will be discussed. This paper focuses on the small synaptic vesicles responsible for fast neuronal transmission. Comparing synaptic vesicles from the peripheral and central nervous systems strengthens the view of a high conservation in the overall composition of synaptic vesicles with a unique set of proteins attributed to this cellular compartment. Synaptic vesicle proteins belong to gene families encoding multiple isoforms present in subpopulations of neurons. The overall architecture of synaptic vesicle proteins is highly conserved during evolution and homologues of these proteins govern the constitutive secretion in yeast. Neurotoxins from different sources helped to identify target proteins of synaptic vesicles and to elucidate the molecular machinery of docking and fusion. Synaptic vesicle proteins and their markers are useful tools for the understanding of the complex life cycle of synaptic vesicles.
Topics: Animals; Carrier Proteins; Cattle; Cholinergic Fibers; Exocytosis; GTP-Binding Proteins; Humans; Neurotransmitter Agents; Rats; Synaptic Membranes; Synaptic Vesicles
PubMed: 7700521
DOI: 10.1016/0306-4522(94)00408-w -
Seminars in Cell & Developmental Biology Jun 2011Synaptic vesicles are organized in clusters, and synapsin maintains vesicle organization and abundance in nerve terminals. At the functional level, vesicles can be... (Review)
Review
Synaptic vesicles are organized in clusters, and synapsin maintains vesicle organization and abundance in nerve terminals. At the functional level, vesicles can be subdivided into three pools: the releasable pool, the recycling pool, and the reserve pool, and synapsin mediates transitions between these pools. Synapsin directs vesicles into the reserve pool, and synapsin II isoform has a primary role in this function. In addition, synapsin actively delivers vesicles to active zones. Finally, synapsin I isoform mediates coupling release events to action potentials at the latest stages of exocytosis. Thus, synapsin is involved in multiple stages of the vesicle cycle, including vesicle clustering, maintaining the reserve pool, vesicle delivery to active zones, and synchronizing release events. These processes are regulated via a dynamic synapsin phosphorylation/dephosphorylation cycle which involves multiple phosphorylation sites and several pathways. Different synapsin isoforms have unique and non-redundant roles in the multifaceted synapsin function.
Topics: Animals; Humans; Nerve Endings; Phosphorylation; Synapses; Synapsins; Synaptic Vesicles
PubMed: 21827866
DOI: 10.1016/j.semcdb.2011.07.003 -
Journal of Physiology, Paris 1993Cholinergic synaptic vesicles contain a mixture of soluble low molecular mass constituents. Besides acetylcholine these include Ca2+, ATP, GTP, small amounts of ADP and... (Review)
Review
Cholinergic synaptic vesicles contain a mixture of soluble low molecular mass constituents. Besides acetylcholine these include Ca2+, ATP, GTP, small amounts of ADP and AMP, and also the diadenosine polyphosphates Ap4A and Ap5A. In synaptic vesicles isolated from the electric ray these diadenosine polyphosphates occur in mmol concentrations and might represent a novel cotransmitter. The membrane proteins of cholinergic synaptic vesicles presumably are identical to those in other types of electron-lucent synaptic vesicles. A presumptive exception are the transmitter-specific carriers. The life cycle of the synaptic vesicle in intact neurons and in situ was investigated by analysis of all cytoplasmic membrane compartments that share membrane integral proteins with synaptic vesicles. The results suggest that the synaptic vesicle membrane compartment might originate from the trans-Golgi network and, after cycles of exo- and endocytosis in the nerve terminal, might fuse into an endosomal membrane compartment early on retrograde transport. Tracer experiments using membrane proteins and soluble contents suggest that the synaptic vesicle membrane compartment does not intermix with the presynaptic plasma membrane on repeated cycles of exo- and endocytosis if low frequency stimulation is applied. A cDNA has been isolated from the electric ray electric lobe that codes for o-rab3, a small GTP-binding protein highly homologous to mammalian rab3. While abundant in the nerve terminals of the electric organ and at the neuromuscular junction this protein occurs only in limited subpopulations of nerve terminals in electric ray brain. Immunocytochemical analysis using the colloidal gold technique and a monospecific antibody against o-rab3 suggests that the GTP-binding protein remains attached to recycling synaptic vesicles. No evidence was found for a major contribution of an intraterminal endosomal sorting compartment involved in synaptic vesicle recycling.
Topics: Acetylcholine; Amino Acid Sequence; Animals; Membrane Proteins; Molecular Sequence Data; Nerve Endings; Sequence Alignment; Solubility; Synapses; Synaptic Vesicles
PubMed: 8136785
DOI: 10.1016/0928-4257(93)90027-q -
Cold Spring Harbor Protocols Jan 2012The synaptic vesicle is the essential organelle of the synapse. Many approaches for studying synaptic vesicle recycling have been devised, one of which, the styryl (FM)... (Review)
Review
The synaptic vesicle is the essential organelle of the synapse. Many approaches for studying synaptic vesicle recycling have been devised, one of which, the styryl (FM) dye, is well suited for this purpose. FM dyes reversibly stain, but do not permeate, membranes; hence they can specifically label membrane-bound organelles. Their quantum yield is drastically higher when bound to membranes than when in aqueous solution. This protocol describes the imaging of synaptic vesicle recycling by staining and destaining vesicles with FM dyes. Nerve terminals are stimulated (electrically or by depolarization with high K(+)) in the presence of dye, their vesicles are then allowed to recycle, and finally dye is washed from the chamber. In neuromuscular junction (NMJ) preparations, movements of the muscle must be inhibited if imaging during stimulation is desired (e.g., by application of curare, a potent acetylcholine receptor inhibitor). The main characteristics of FM dyes are also reviewed here, as are recent FM dye monitoring techniques that have been used to investigate the kinetics of synaptic vesicle fusion.
Topics: Animals; Cytological Techniques; Fluorescent Dyes; Humans; Pyridinium Compounds; Specimen Handling; Synaptic Vesicles
PubMed: 22194270
DOI: 10.1101/pdb.prot067603 -
Cellular and Molecular Life Sciences :... Sep 2008Vesicular transport is the basic communication mechanism between different compartments in a cell and with the environment. In this review I discuss the principles of... (Review)
Review
Vesicular transport is the basic communication mechanism between different compartments in a cell and with the environment. In this review I discuss the principles of vesicle generation and consumption with particular emphasis on the different types of coat proteins and the timing of the shedding of the coat proteins from transport containers. In recent years it has become clear that there are more coat complexes than the classical COPI, COPII and clathrin coats. These additional coats may generate vesicles that transport cargo in a temporally and/or spatially controlled manner. Work over the last years suggests that GTP hydrolysis occurs early during vesicle biogenesis, destabilizing the coat perhaps before fission of the vesicle from the donor membrane occurs. Recent findings imply, however, that tethers at the receiving compartment specifically detect the coat on vesicle.
Topics: ADP-Ribosylation Factors; Animals; Biological Transport; Cell Membrane; Coated Vesicles; Guanosine Triphosphate; Intracellular Membranes; SNARE Proteins; Transport Vesicles; Vesicular Transport Proteins
PubMed: 18726180
DOI: 10.1007/s00018-008-8349-y -
Seminars in Cell & Developmental Biology Apr 2015Extracellular vesicles including exosomes, microvesicles and apoptotic vesicles, are phospholipid bilayer surrounded structures secreted by cells universally, in an... (Review)
Review
Extracellular vesicles including exosomes, microvesicles and apoptotic vesicles, are phospholipid bilayer surrounded structures secreted by cells universally, in an evolutionarily conserved fashion. Posttranslational modifications such as oxidation, citrullination, phosphorylation and glycosylation play diverse roles in extracellular vesicle biology. Posttranslational modifications orchestrate the biogenesis of extracellular vesicles. The signals extracellular vesicles transmit between cells also often function via modulating posttranslational modifications of target molecules, given that extracellular vesicles are carriers of several active enzymes catalysing posttranslational modifications. Posttranslational modifications of extracellular vesicles can also contribute to disease pathology by e.g. amplifying inflammation, generating neoepitopes or carrying neoepitopes themselves.
Topics: Animals; Citrulline; Extracellular Vesicles; Glycosylation; Humans; Oxidation-Reduction; Phosphorylation; Protein Processing, Post-Translational; Ubiquitination
PubMed: 25721811
DOI: 10.1016/j.semcdb.2015.02.012 -
Nature Jun 1995The synaptic vesicle cycle at the nerve terminal consists of vesicle exocytosis with neurotransmitter release, endocytosis of empty vesicles, and regeneration of fresh... (Review)
Review
The synaptic vesicle cycle at the nerve terminal consists of vesicle exocytosis with neurotransmitter release, endocytosis of empty vesicles, and regeneration of fresh vesicles. Of all cellular transport pathways, the synaptic vesicle cycle is the fastest and the most tightly regulated. A convergence of results now allows formulation of molecular models for key steps of the cycle. These developments may form the basis for a mechanistic understanding of higher neural function.
Topics: Animals; Bacterial Toxins; Calcium-Binding Proteins; Endocytosis; Exocytosis; GTP-Binding Proteins; Humans; Membrane Fusion; Membrane Glycoproteins; Nerve Tissue Proteins; Neuronal Plasticity; Synaptic Vesicles; Synaptotagmins; rab3 GTP-Binding Proteins
PubMed: 7791897
DOI: 10.1038/375645a0 -
Cell Biology International Reports Dec 1989The paper discusses functional and molecular aspects of the synaptic vesicle membrane during its life cycle. The distribution of the synaptic vesicle membrane... (Review)
Review
The paper discusses functional and molecular aspects of the synaptic vesicle membrane during its life cycle. The distribution of the synaptic vesicle membrane compartment in an entire cholinergic neuron is monitored using colloidal gold labelling and a monoclonal antibody against the synaptic vesicle membrane protein SV2. This provides new insights concerning vesicle origin and fate in the various compartments of the neuron. A new synaptic vesicle membrane protein (svp25) of Mr 25,000 with properties similar to synaptophysin as well as a synaptic vesicle binding phosphoprotein of the presynaptic membrane (Mr 92,000) likely to be involved in vesicle exocytosis are described. The membrane compartment recycled on induced transmitter release contains synaptic vesicle but not plasma membrane markers and encloses both newly synthesized transmitter and a sample of extracellular medium.
Topics: Animals; Exocytosis; Membrane Proteins; Neurons; Synaptic Vesicles
PubMed: 2699837
DOI: 10.1016/0309-1651(89)90015-5 -
Applied and Environmental Microbiology Dec 2022The exchange of bacterial extracellular vesicles facilitates molecular exchange between cells, including the horizontal transfer of genetic material. Given the...
The exchange of bacterial extracellular vesicles facilitates molecular exchange between cells, including the horizontal transfer of genetic material. Given the implications of such transfer events on cell physiology and adaptation, some bacterial cells have likely evolved mechanisms to regulate vesicle exchange. Past work has identified mechanisms that influence the formation of extracellular vesicles, including the production of small molecules that modulate membrane structure; however, whether these mechanisms also modulate vesicle uptake and have an overall impact on the rate of vesicle exchange is unknown. Here, we show that membrane-binding molecules produced by microbes influence both the formation and uptake of extracellular vesicles and have the overall impact of increasing the vesicle exchange rate within a bacterial coculture. In effect, production of compounds that increase vesicle exchange rates encourage gene exchange between neighboring cells. The ability of several membrane-binding compounds to increase vesicle exchange was demonstrated. Three of these compounds, nisin, colistin, and polymyxin B, are antimicrobial peptides added at sub-inhibitory concentrations. These results suggest that a potential function of exogenous compounds that bind to membranes may be the regulation of vesicle exchange between cells. The exchange of bacterial extracellular vesicles is one route of gene transfer between bacteria, although it was unclear if bacteria developed strategies to modulate the rate of gene transfer within vesicles. In eukaryotes, there are many examples of specialized molecules that have evolved to facilitate the production, loading, and uptake of vesicles. Recent work with bacteria has shown that some small molecules influence membrane curvature and induce vesicle formation. Here, we show that similar compounds facilitate vesicle uptake, thereby increasing the overall rate of vesicle exchange within bacterial populations. The addition of membrane-binding compounds, several of them antibiotics at subinhibitory concentrations, to a bacterial coculture increased the rate of horizontal gene transfer via vesicle exchange.
Topics: Bacteria; Gene Transfer, Horizontal; Extracellular Vesicles; Membranes; Eukaryota
PubMed: 36342184
DOI: 10.1128/aem.01346-22 -
Biochemical Society Transactions Aug 2003SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex formation between a vesicle and the target membrane is a central aspect of probably... (Review)
Review
SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex formation between a vesicle and the target membrane is a central aspect of probably all vesicle fusion reactions. The sec1/munc18 (SM) protein family is also involved in membrane trafficking and fusion events. However, in contrast with the consensus on SNARE protein function, analysis of SM proteins in different systems has produced different ideas about their exact role, their site of action and their relationship to SNARE proteins. Deletion of the SM protein involved in secretory vesicle release in mice, Munc18-1, results in a complete block of exocytosis. Manipulation of Munc18-1 protein levels in neurons and adrenal chromaffin cells argues for a positive role of this protein in vesicle secretion, as overexpression results in an increase in vesicle secretion. A decrease in Munc18-1 protein levels, on the other hand, leads to a decrease in vesicle secretion.
Topics: Animals; Antigens, Surface; Munc18 Proteins; Mutation; Nerve Tissue Proteins; Phenotype; Proteins; Secretory Vesicles; Synaptic Vesicles; Syntaxin 1; Vesicular Transport Proteins
PubMed: 12887319
DOI: 10.1042/bst0310848