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We report here a detailed characterisation of the conformational properties of αS bound to the inner and outer leaflets of the presynaptic plasma membrane (PM), using small unilamellar vesicles. (cam.ac.uk)
In SK-N-SH cells, carbachol induced a rapid and transient translocation of tubulin to the plasma membrane, microtubule reorganization, and a change in cell shape as demonstrated by confocal immunofluorescence microscopy. (jneurosci.org)
It mediates fusion of synaptic vesicles with the presynaptic plasma membrane resulting in exocytosis of neurotransmitters. (nature.com)
He concludes that the ultrafast mechanism is not a kiss-and-run model and the slow mechanism does not operate at the plasma membrane, as the clathrin model is thought to. (eurekalert.org)
During endocytosis, extracellular molecules and plasma membrane components are selectively internalized by cells. (cshlpress.com)
Using postmortem brain tissues from an INCL patient and tissue from the PPT1-knockout (PPT1-KO) mice that mimic INCL, we report here that PPT1 deficiency caused persistent membrane anchorage of the palmitoylated SV proteins, which hindered the recycling of the vesicle components that normally fuse with the presynaptic plasma membrane during SV exocytosis. (jci.org)
Upon maturation, the rate of endocytosis is reduced, and a cAMP-dependent neuronal signal triggers the transport of PLP from LEs/Ls to the plasma membrane. (rupress.org)
ii) co-operating with SNAREs to promote synaptic vesicle fusion at the plasma membrane. (anr.fr)
This release is based on exocytosis: The vesicle docks at the cell membrane, opens at the point of contact, releases part of its contents to the outside, closes, and separates from the plasma membrane so it can be refilled. (news-medical.net)
Before and after the opening of the vesicle a pore forms at the point of contact with the plasma membrane. (news-medical.net)

These effects are accompanied by imbalances in the activity of specific prenylated proteins, Rab3 and RhoA, involved in neurotransmitter release, and synaptic plasticity, respectively. (nature.com)
Prenylation, the covalent binding of farnesyl pyrophosphate (FPP) or geranylgeranyl pyrophosphate (GGPP) moieties to proteins, is a crucial post-translational modification for the regulation of protein localization on cell membranes and, in turn, for key cellular processes. (nature.com)
This gene product belongs to the SCAMP family of proteins, which are secretory carrier membrane proteins. (nih.gov)
Synaptotagmins are membrane proteins that are important in neurotransmission and hormone secretion, both of which involve regulated exocytosis. (nih.gov)
In particular, polymer-encapsulated nanodiscs enable the study of membrane proteins at high resolution while retaining protein-protein and protein-lip. (researchgate.net)
High-Precision Mapping of Membrane Proteins on Synaptic Vesicles using Spectrally Encoded Super-Resolution Imaging. (harvard.edu)
Neurotransmission relies on repeated cycles of exo- and endocytosis of the synaptic vesicles (SVs), in which several palmitoylated proteins play critical roles. (jci.org)
These proteins facilitate membrane fusion, which is required for neurotransmitter exocytosis, recycling of the fused SV membrane components, and regeneration of fresh vesicles. (jci.org)
These proteins - which drive various membrane remodeling events such as fission reactions that release intralumenal vesicles into endosomes and viruses from the cell surface -are one of Phylllis Hanson's many research interests. (asbmb.org)
My long-term overall interest is in the cell biology of molecular machines, with a particular interest in understanding how proteins regulate the structure and organization of membranes, both inside and outside the cell. (asbmb.org)
As a postdoc, I wanted to learn more about the nuts and bolts of synapses and moved to study the biochemistry of proteins responsible for synaptic vesicle trafficking. (asbmb.org)
The C2 domain is a Ca 2+ -dependent membrane-targeting module found in many cellular proteins involved in signal transduction or membrane trafficking. (embl.de)
separation of proteins by PAGE and subsequent transfer to a membrane. (sysy.com)
B.ll.2 Interaction of Ca" Channels with Synaptic Vesicle Proteins Neurotransmitter release is to form a synaptic core complex (SNARE), which mediates vesicle docking and membrane fusion. (addresources.org)

Work from several laboratories including my own has found that the curvature-sensing protein endophilin plays a critical role in synaptic vesicle endocytosis. (hhs.gov)
2) We will study how curvature signals are received by the downstream protein synaptojanin to support synaptic vesicle endocytosis, and to prevent age-dependent decay of synaptic transmission. (hhs.gov)
Single-molecule analysis of protein conformational change in membrane environment (membrane property change induced by protein) and Nanotechnology (nanoparticle structures for biomedical detection). (uc.edu)
Because most tubulin is not membrane associated, this study investigates whether tubulin translocates to the membrane in response to an agonist so that it might regulate G-protein signaling. (jneurosci.org)
To achieve this, the neuronal SNARE (i.e., soluble N -ethylmaleimide-sensitive factor attachment protein receptor) complex brings the vesicle and presynaptic membranes in close proximity, thereby, mediating the fusion of the two membranes resulting in exocytosis of neurotransmitters. (nature.com)
Fusion of synaptic vesicles with the presynaptic membrane occurs in the presence of the NSF (N-ethylmaleimide-sensitive-factor) / α-SNAP (α-soluble NSF attachment protein) disassembly machinery. (nature.com)
New technologies for purifying membrane-bound protein complexes in combination with cryo-electron microscopy (EM) have recently allowed the exploration of such complexes under near-native conditions. (researchgate.net)
Scientists have previously proposed two models by which vesicle recycling happens--a faster model called kiss-and-run and a slower model based on the protein clathrin. (eurekalert.org)
have shown that another protein, synaptotagmin 7, also has a key role in the replenishment of synaptic vesicles, possibly as a sensor for calcium ions. (elifesciences.org)
After two decades researching protein-protein and protein-membrane interactions involved in membrane trafficking at WUSTL, Hanson recently moved her lab to the University of Michigan Medical School's department of biochemistry - which she now chairs . (asbmb.org)
These include SNAREs, which mediate vesicle function, and NSF, a AAA+ ATPase that maintains protein dynamics of the SNAREs, and thus membrane trafficking. (asbmb.org)
Synaptophysin is an integral membrane protein involved in neurotransmitter exocytosis. (enzolifesciences.com)
Studies have shown Synaptophysin to be a major cholesterol-binding protein in brain synaptic vesicles. (enzolifesciences.com)
Synaptic vesicle membrane protein VAT-1 homolog is a protein that in humans is encoded by the VAT1 gene . (wn.com)
The protein encoded by this gene is an abundant integral membrane protein of cholinergic synaptic vesicles and is thought to be involved in vesicular transport. (wn.com)
We have found that the C-terminal systeine residues of smg p21B, rhoA p21, and smg p25A are geranylgeranylated, and that these prenylation are essential for each small G protein to bind to membranes. (nii.ac.jp)
Publications] Araki,S.: 'Role of the Cーterminal region of smg p25A in its interaction with membranes and the GDP/GTP exchange protein. (nii.ac.jp)
Misfolding of the protein alpha-synuclein (aS), which associates with presynaptic vesicles, has been implicated in the molecular chain of events leading to Parkinson's disease. (rcsb.org)
In the absence of neurons, the major myelin membrane protein, the proteolipid protein (PLP), is internalized and stored in late endosomes/lysosomes (LEs/Ls) by a cholesterol-dependent and clathrin-independent endocytosis pathway that requires actin and the RhoA guanosine triphosphatase. (rupress.org)
The experiment used genetically modified mice that had a light sensitive protein, usually found in the eye, embedded in the membrane of the presynaptic neurons in one area of the brain (purple circle). (oist.jp)
The former is capable of binding to protein kinase C, an enzyme that binds to the membrane to regulate the speed of exocytosis. (news-medical.net)
The zinc species inside the cell could slow down the transport protein that loads the dopamine into the vesicles," suggests Ewing. (news-medical.net)
Around 60-80% of cases1 are caused by mutations of the gene that encodes optic atrophy protein 1 (OPA1), a protein that has a key role in inner mitochondrial membrane fusion and remodelling of cristae and is crucial for the dynamic organization and regulation of mitochondria2. (bvsalud.org)
The pre-synaptic protein α-synuclein (α-syn) can be found in amyloid plaques in patients with Parkinson's Disease (PD). (lu.se)

The history of the field will be briefly reviewed, focusing on exocytosis and membrane fusion. (sfn.org)
In the control frog, in the same type of synaptic terminal, the vesicles were divided from the presynaptic membrane by well-defined dense projections, exocytosis profiles were observed only in LSD-treated frogs. (erowid.org)
In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. (bvsalud.org)
Membrane fusion generates an opening through which the molecules are expelled into the synaptic cleft via exocytosis. (msdmanuals.com)

Signal transmission in neurons is accomplished by neurotransmitter release from the lumen of synaptic vesicles into the synaptic cleft of synapses where they are received by postsynaptic receptors 1 . (nature.com)
3) This causes synaptic vesicles to fuse with the terminal membrane, releasing neurotransmitter into the gap between neurons, known as the synaptic cleft. (oist.jp)
When signals are transmitted by synapses, messenger molecules (neurotransmitters) are released from storage chambers (synaptic vesicles) into the synaptic cleft, where they are "recognized" by neighboring nerve cells. (news-medical.net)
Normal neuromuscular junction showing a presynaptic terminal with a motor nerve ending in an enlargement (bouton terminale): Synaptic cleft and postsynaptic membrane with multiple folds and embedded with several acetylcholine receptors. (medscape.com)
Neurotransmitters diffuse across the synaptic cleft and bind briefly to specific receptors on the adjoining neuron or effector cell. (msdmanuals.com)

To better understand how our nervous system sustains their activities to meet our physical and mental demands, Watanabe and his colleagues at the University of Utah have been studying how neurons recycle synaptic vesicles, small cellular structures that store neurotransmitters, the primary means of communication between neurons. (eurekalert.org)
After neurons are stimulated, synaptic vesicles fuse with the cell membrane, releasing their chemical signals, neurotransmitters. (eurekalert.org)
The synaptic terminals of the transmitting neuron (the presynaptic element) send signals by releasing chemical molecules (neurotransmitters) to the dendritic, somatic or axonic, part of the receiving neuron (postsynaptic term) [ 3 ]. (biomedcentral.com)
In the following decades, recycling routes for synaptic vesicle and for neurotransmitters were worked out, but only since the mid-1980s are the molecular mechanisms governing the steps in synaptic vesicle cycling becoming known. (sfn.org)
Synaptic vesicles are responsible for regulating the storage and release of neurotransmitters in the nerve terminal. (wn.com)
When an electrical nerve impulse, or action potential, arrives at the end of the presynaptic neuron, this causes synaptic vesicles - tiny membrane 'packets' that contain neurotransmitters - to fuse with the terminal membrane, releasing the neurotransmitters into the gap between neurons. (oist.jp)
4) The neurotransmitters bind to receptor sites on ion channels in the postsynaptic membrane, causing them to open. (oist.jp)

Motivated by the need to address some aspects of the functioning of neural synapses, we have developed one such model for synaptic processes in the calyx of Held , which is a glutamatergic synapse in the auditory pathway of the mammalia. (biomedcentral.com)
At chemical synapses, depolarization-induced calcium influx triggers neurotransmitter release, a key step in synaptic signaling. (sfn.org)
Calretinin-Expressing Synapses Show Improved Synaptic Efficacy with Reduced Asynchronous Release during High-Rate Activity. (sysy.com)

Functionally, synaptic vesicle endocytosis allows neurons to sustain synaptic transmission without exhausting the supply of synaptic vesicles. (hhs.gov)
Together with Syntaxin-1A and SNAP25, it forms the core membrane fusion machinery that is responsible for neurotransmitter release and, therefore, signal transmission between neurons. (researchgate.net)
when light flashes, neurons engineered to express channelrhodopsin are activated, causing the synaptic vesicles they harbor to fuse at nerve terminals. (eurekalert.org)
Following a fusion event, neurons must replenish their vesicle stocks to ensure that they are ready for the arrival of the next action potential. (elifesciences.org)
In this study, we show that neurons regulate myelin membrane trafficking in oligodendrocytes. (rupress.org)

The SNARE complex assembles from vesicular Synaptobrevin-2 as well as Syntaxin-1 and SNAP25 both anchored to the presynaptic membrane. (nature.com)
Zippering of the SNAREs is proposed to provide the required energy to initiate membrane fusion 6 , 7 and proceeds from the N-terminus towards the membrane-proximal C-terminus through interactions of their complementary SNARE motifs. (nature.com)
At the molecular level we will dissect interactions between the V-ATPase membrane sector and the SNARE membrane fusion machinery and design probes to assess their functional relevance. (anr.fr)

Surprisingly, FM1-43 labeling indicates normal exo- and endocytosis, but a specific inability to mobilize reserve pool vesicles, which is partially rescued by exogenous ATP. (nih.gov)
As a result, defective synaptic vesicle endocytosis creates deficits in neurotransmission that underlie a wide spectrum of neurological diseases and psychiatric disorders. (hhs.gov)
We focus on the curvature-sensing amphipathic helix of endophilin as it is essential for synaptic vesicle endocytosis. (hhs.gov)

Montal 2010), acidification, a normal step in synaptic vesicle recycling, is inferred to cause a conformational change in the botulinum toxin type G disulfide-bonded heavy chain - light chain dimer (BoNT/G HC:LC) it contains, allowing the HC part of the toxin to function as a channel through which its LC part is extruded into the neuronal cytosol. (reactome.org)

The neurotransmitter molecules are stored in the first cell in packages known as vesicles, which release their contents by fusing with the cell membrane. (elifesciences.org)
As reported in the journal Angewandte Chemie, zinc changes the number of messenger molecules stored in vesicles and the dynamics of their release from the cell. (news-medical.net)
By applying an electrode tip to the surface of the cell, we can follow the opening of an individual vesicle and compute the number of molecules released," says Ewing. (news-medical.net)
Says Ewing: "The current transients allow us to determine how many transmitter molecules are contained in individual vesicles directly in the cytoplasm of the living cells. (news-medical.net)
The vesicle thus stays open longer and releases 92 % of its transmitter molecules to the outside-instead of only 66 % without the zinc. (news-medical.net)
Membrane-bound compartments which contain transmitter molecules. (bvsalud.org)
The amount in one vesicle (usually several thousand molecules) is a quantum. (msdmanuals.com)
calcium inflow releases neurotransmitter molecules from many vesicles by fusing the vesicle membranes to the nerve terminal membrane. (msdmanuals.com)

Most cases are due to immunoglobulin G1 (IgG1) and IgG3 antibodies that attack AChR in the postsynaptic membrane, causing complement-mediated damage and muscle weakness. (wikipedia.org)

In general, each neuron consists of a somatic cellular body, on which a variable number of thin elongated structures, called dendrites, converge and from which a long single structure, called axon, emerges, branching in several synaptic terminals. (biomedcentral.com)
In LSD treated frogs, the density of synaptic vesicles in same terminals was low. (erowid.org)
This could be due to the type of fixation as in the control frog some synaptic terminals had a low density of vesicles. (erowid.org)
Synaptic vesicles are concentrated at presynaptic terminals. (bvsalud.org)

Sensitivity analysis over several parameters of the model has provided results that may help clarify the dynamics of synaptic transmission, while experiments with the model of the complete synapse seem worth explaining short-term plasticity mechanisms. (biomedcentral.com)
In the long term, we are interested, in particular, in addressing models of synaptic plasticity, i.e. activity dependent mechanisms, which are the bases of memory and learning processes. (biomedcentral.com)

Early in his research career, Stevens sought to understand the molecular mechanisms of how electrical currents travel through ion channels during synaptic transmission, and the role such transmission plays in learning and memory. (the-scientist.com)
A cost-benefit analysis of the physical mechanisms of membrane curvature. (academictree.org)

The pair published a paper in 1977 about statistical fluctuations in recordings of the ionic pores of neuron membranes. (the-scientist.com)

We have now found that synaptotagmin is capable of pulling the synaptic vesicles closer to the membrane within a matter of milliseconds. (charite.de)
Shuwen Chang, Thorsten Trimbuch, Christian Rosenmund: Synaptotagmin-1 drives synchronous Ca2+-triggered fusion by C2B-domain-mediated synaptic-vesicle-membrane attachment. (charite.de)

Here, incoming signals effect the release of transmitters from stores known as 'vesicles', which fuse with the adjoining cell membranes in order to transmit the signal. (charite.de)

Classically the V-ATPase is a proton pump that ensures the acidification of intracellular compartments, including those destined for secretion and notably synaptic vesicles. (anr.fr)
A molecular understanding of membrane traffic has broad implications for our understanding of growth control in cancer, receptor trafficking errors in heart disease, regulation of insulin secretion in diabetes and synaptic vesicle biogenesis and transport in neurological disorders. (stanford.edu)

The majority of cholesterol is present in myelin sheaths and in neuronal membranes, where this lipid fulfills structural and functional tasks. (nature.com)
C2 domains are unique among membrane targeting domains in that they show wide range of lipid selectivity for the major components of cell membranes, including phosphatidylserine and phosphatidylcholine. (embl.de)
The aim of my project is to use fluorescence microscopy to obtain information about possible vesicle fusion and exchange of lipids between single, fluorescently labelled lipid vesicles, both due to interactions with α -syn. (lu.se)
Lipid exchange or fusion between two vesicles labeled with different dyes can be detected by colocalization of the dyes and the appearance of a fret signal when exciting the donor dye. (lu.se)

The vesicular monoamine transporter acts to accumulate cytosolic monoamines into synaptic vesicles,using the proton gradient maintained across the synaptic vesicular membrane. (origene.com)

I used a set of enzymes, AAA+ ATPases, as my group's entry point, because I knew how to study them and could see that key members, including the ESCRT-regulatory AAA+ ATPase VPS4 and the dystonia-associated AAA+ ATPase torsinA, were regulating cellular membranes in different and unexpected ways. (asbmb.org)
Participates in a variety of cellular processes such as vesicle mediated transport, cell adhesion, cell polarization and cell migration. (nih.gov)
the anesthetic had the strongest effect on higher frequency impulses that are required for functions such as cognition or movement, whilst it had minimal effect on low frequency impulses that control life-supporting functions, such as breathing," said Professor Tomoyuki Takahashi, who leads the Cellular and Molecular Synaptic Function (CMSF) Unit at OIST. (oist.jp)

Chemical cross-linking provides detailed insights into these interactions suggesting a role for membrane fusion. (nature.com)
The ultrafast mechanism perhaps rapidly clears the fusion sites of excess membrane," he wrote. (eurekalert.org)
In neuronal membrane for fusion to occur, which allows the nerve impulse to be delivered across the synaptic junction. (cdc.gov)
In short, the distance between the synaptic vesicle and the membrane is a major barrier to rapid fusion," explains the article's corresponding author, Prof. Dr. Christian Rosenmund of the Institute of Neurophysiology and the NeuroCure Cluster of Excellence. (charite.de)
It does this by acting like a double-sided sticky tape, forming a bridge between the vesicle and the membrane," says Prof. Rosenmund, further explaining that fusion can only occur once this bridge has been formed. (charite.de)
Dr. Shuwen Chang, a researcher at the Rosenmund Lab and the study's first author, was meant to use the new electron microscopy-based method for the direct visualization of the vesicle-membrane fusion process. (charite.de)
They were surprised to find that this not only slowed the process of fusion, but also resulted in vesicles and membranes remaining farther apart. (charite.de)
The researchers are planning to conduct further experiments in the hope of establishing whether these mutations also affect the speed of vesicle fusion and, consequently, the speed at which nerve cells communicate. (charite.de)
Many years ago, I read a review article about membrane fusion, which I was working on at the time, with a title that raised the ever-present question of mimicry and mechanism in model systems. (asbmb.org)
Our project is based on accumulating, evidence that the membrane sector of the V-ATPase also acts at a late step in membrane fusion. (anr.fr)
It is possible to distinguish between fusion and exchange since a fusion event would lead to fewer but larger vesicles with higher fluorescence intensities, while an exchange event would lead to an unchanged number of vesicles with lower fluorescence intensities of respective dye. (lu.se)

M uch of our modern understanding of the mechanics of synaptic transmission and the highly conserved organization of neural networks in vertebrate brains comes from Charles "Chuck" Stevens. (the-scientist.com)

Clathrin light chain diversity regulates membrane deformation in vitro and synaptic vesicle formation in vivo. (academictree.org)

We were able to capture snapshots of the events at different time points, in effect, generating a 'flip-book' of membrane movement during synaptic transmission with millisecond temporal resolution, Watanabe said. (eurekalert.org)
Activation results in membrane hyperexcitability, spontaneous repetitive neurotransmitter release, blockage of synaptic transmission, and depletion of synaptic vesicles. (medscape.com)

A specific and time-dependent association of tubulin with plasma membranes was observed when SK-N-SH cells were treated with carbachol. (jneurosci.org)
The same phenomenon was observed with membranes from Sf9 cells, expressing a recombinant PLCβ 1 cascade. (jneurosci.org)
Moreover, we identify a distinct, N-terminal, higher affinity interaction interface between LRRK2 phosphorylated Rab8 and Rab10 termed 'Site #2', that can retain LRRK2 on membranes in cells to catalyze multiple, subsequent phosphorylation events. (stanford.edu)

Here, we resolved Ca 2+ -dependent and Ca 2+ -independent synaptic vesicle (SV) replenishment pathways, and found that syt 7 plays a selective and critical role in the Ca 2+ -dependent pathway. (elifesciences.org)

Results from these studies are expected to to push boundaries of current knowledge of synaptic biology and to lead toward solutions for neurological disorders. (hhs.gov)

The C2 domain is thought to be involved in calcium-dependent phospholipid binding [ ( PUBMED:8253763 ) ] and in membrane targetting processes such as subcellular localisation. (embl.de)

Topics such as lysosomal dynamics, the biophysical challenges of bending membranes, and the evolution of endocytic systems are also covered. (cshlpress.com)
These unusually rich dynamics may serve to mitigate the effect of aS binding on membrane fluidity. (rcsb.org)

The functional role of αS is still debated, although it has been involved in the regulation of neurotransmitter release via the interaction with synaptic vesicles (SVs). (cam.ac.uk)
The well ordered conformation of the helix-helix connector indicates a defined interaction with lipidic surfaces, suggesting that, when bound to larger diameter synaptic vesicles, it can act as a switch between this structure and a previously proposed uninterrupted helix. (rcsb.org)
An important event seems to be the interaction between a -syn and lipids, which are the main building block of the membrane surrounding each cell. (lu.se)

During vertebrate brain development, axons are enwrapped by myelin, an insulating membrane produced by oligodendrocytes. (rupress.org)

The slower mechanism, a clathrin-dependent process, reconstitutes vesicles at a more leisurely pace from endosomes--nevertheless it only requires 2-3 seconds, which is considered rapid for any mechanism. (eurekalert.org)

In LSD-treated frogs the vesicles were often aligned in rows which seemed to follow a preferential pathway towards the presynaptic membrane, onto which they closely adhered. (erowid.org)
A feed-forward pathway drives LRRK2 kinase membrane recruitment and activation. (stanford.edu)

The researchers found one zinc species near the cell membrane and a second in the interior of the cell. (news-medical.net)

scientists had previously thought that synaptic vesicles were regenerated at the cell surface. (eurekalert.org)
We're looking at their role in an increasingly huge range of cell biological processes, and we're particularly excited right now about a recent discovery that the ESCRT machinery responds to and facilitates the repair of super-small-scale damage in membranes that can be caused by any number of insults from the environment. (asbmb.org)
In contrast, if the tip of the electrode is inserted into the cell, the vesicles in the cytoplasm stick to the electrode and release their full contents. (news-medical.net)

Using a variety of drugs, we provide evidence that reserve pool recruitment depends on mitochondrial ATP production downstream of PKA signaling and that mitochondrial ATP limits myosin-propelled mobilization of reserve pool vesicles. (nih.gov)

In the 1950s, Katz found that transmitter release is quantal, and synaptic vesicles were discovered. (sfn.org)

Anatomy58

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