• Cleavage of any one of the three neuronal SNARE proteins blocks fusion of synaptic vesicles to plasma membranes, thus preventing neurotransmitter release from neurons. (nature.com)
  • In neurons, inhibition of endocytosis results in depletion of vesicles and abolition of synaptic transmission . (tocris.com)
  • A MARVEL domain-containing protein found in the presynaptic vesicles of NEURONS and NEUROENDOCRINE CELLS . (bvsalud.org)
  • The toxin is taken up into clathrin-coated vesicles that reach the neuron cell body by retrograde transport and then possibly other neurons before undergoing acidification. (reactome.org)
  • To solve this, we analyzed the motion of 45 GFP-tagged synaptic proteins expressed in cultured hippocampal neurons, using fluorescence recovery after photobleaching, particle tracking, and modeling. (units.it)
  • To communicate with each other, neurons can use chemical synaptic transmission. (hstalks.com)
  • In the brain, EAATs remove glutamate from the synaptic cleft and extrasynaptic sites by glutamate reuptake into glial cells and neurons, while VGLUTs "load" glutamate from the cytoplasm of neuronal cells into synaptic vesicles. (sysy.com)
  • Vesicle cycle at the synaptic cleft of glutamatergic neurons. (sysy.com)
  • Several membrane proteins and lipids interact with Aβ affecting its toxicity in neurons. (marquette.edu)
  • Because previous studies have recognized that Aβ oligomers are able to increase membrane permeability and produce amyloid pores, the present study supports the conclusion that NMDARs play a critical protective role on Aβ actions in hippocampal neurons. (marquette.edu)
  • shRNA-mediated knockdown of the AP-2 complex results in an approximately 96% reduction of this protein complex in primary neurons. (cornell.edu)
  • Like Aβ oligomers, soluble aggregates of tau and α-synuclein bind to cellular prion protein, poisoning neurons, according to a study published in Acta Neuropathologica. (alzforum.org)
  • This toxicity was PrP-dependent: Mouse and human neurons that lacked the prion protein showed no signs of neurite damage. (alzforum.org)
  • These results suggest that reactive oxygen species generated by oxidative stress are detrimental to neurons, resulting in the oxidation of SNARE proteins, thereby disrupting neurotransmission. (elsevierpure.com)
  • Type B toxin acts on vesicle-associated membrane protein synaptobrevin, a membrane protein of small synaptic vesicles. (medscape.com)
  • This gene is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. (nih.gov)
  • Synaptobrevin on the synaptic vesicle must interact with syntaxin and SNAP (synaptosomal-associated protein)-25 on the neuronal membrane for fusion to occur, which allows the nerve impulse to be delivered across the synaptic junction. (cdc.gov)
  • From NCBI Gene: This gene encodes an integral membrane protein that belongs to the synaptobrevin/vesicle-associated membrane protein subfamily of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). (nih.gov)
  • The SNARE proteins, synaptobrevin, SNAP-25, and syntaxin, are involved in the fusion of these two double lipid membranes, which finally elicits the release of neurotransmitter. (hstalks.com)
  • To elucidate whether oxidative stress induces denaturation of SNARE proteins, and whether vitamin E can counteract this process, changes in the expression of synaptobrevin, synaptotagmin, SNAP-25, and syntaxin-1 in rat brain nerve terminals were analyzed using an immunoblotting method. (elsevierpure.com)
  • The results showed that oxidative stress induced significant reductions in the levels synaptobrevin and synaptotagmin in synaptic vesicles. (elsevierpure.com)
  • SV proÂ-teins other than synaptobrevin are summarized as 'cargo proteins' (taken from Haucke et al. (sfb958.de)
  • Endocytosis is the uptake or internalization of material by a cell, through the formation of a membrane bound vesicle. (tocris.com)
  • The process of endocytosis involves the folding of the plasma membrane, creating membrane invaginations containing the particles to be internalized. (tocris.com)
  • Endocytosis is important in metabolism, as it mediates the uptake of nutrients, and the process is also crucial in control of cell surface receptor levels, plasma membrane turnover and cell signaling. (tocris.com)
  • Endophilin is a membrane-binding protein with curvature-generating and -sensing properties that participates in clathrin-dependent endocytosis of synaptic vesicle membranes. (ox.ac.uk)
  • Implicated in synaptic vesicle endocytosis. (nih.gov)
  • Step 2: After the endocytosis of the vesicle the high extracellular concentration of chloride ions (Cl - ) is trapped in the vesicle. (sysy.com)
  • In addition, synaptotagmin appears to be involved in docking and priming (by clamping spontaneous fusion) of synaptic vesicles and regulating fusion pores as well as vesicle endocytosis. (elsevierpure.com)
  • Here, we have investigated its role in synaptic vesicle endocytosis. (cornell.edu)
  • We used simultaneous expression of shRNA and pHluorin-tagged vesicle components to show that the absence of AP-2 significantly slows but does not prevent the endocytosis of four of the major synaptic vesicle transmembrane proteins. (cornell.edu)
  • Classical dynamins (DNMs) are GTPase proteins engaged in endocytosis, a fundamental process for cargo internalization from the plasma membrane. (inrae.fr)
  • Following exocytic fusion SVs are recycled locally (1) (Figure 1) largely via clathrin-mediated endocytosis (CME) of SV proteins within the surrounding periactive zone. (sfb958.de)
  • All of the botulinum toxin serotypes interfere with the activity of soluble N -ethylmaleimide sensitive factor attachment protein receptor (SNARE) proteins, which are involved in the release of acetylcholine at the neuromuscular junction. (medscape.com)
  • Another hypothesis is that SYT mediates Ca 2+ interactions with SNARE proteins and facilitates the fusion process by providing Ca 2+ ions to the synaptic vesicle fusion apparatus [4, 5]. (aiche.org)
  • In this work, molecular dynamics simulations used to understand the interactions of SYT with phospholipid bilayers and SNARE proteins in an effort to elucidate the process of membrane fusion at the atomic level. (aiche.org)
  • Simulations are also used to understand the hypothesized binding of SYT to the tv-SNARE complex during membrane fusion. (aiche.org)
  • Synaptic vesicles fuse with plasma membranes and specifically target snare protein s in the nerve terminal. (freshmediq.com)
  • Additional mutations that alter the interaction between SNAP-25 C-terminal coil and the other SNARE coils dramatically reduce transmitter release probability but leave the kinetics of synaptic responses unaltered. (jneurosci.org)
  • Exactly how the structures of the SNARE molecules relate to their function in synaptic vesicle fusion is under active investigation. (jneurosci.org)
  • highly specific proteases that cleave individual SNARE proteins, have been used extensively as a powerful tool to examine the function of toxin-cleaved SNARE proteins during neuromuscular or CNS synaptic transmission, as well as for chromaffin cell secretion. (jneurosci.org)
  • Synaptotagmin also binds to the soluble Nethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex that is believed to be the core fusion machinery, although the findings on the Ca 2+ dependency of binding of synaptotagmin to SNARE have been inconsistent and controversial. (elsevierpure.com)
  • The process of fusing synaptic plasma membranes and synaptic vesicles involves particular proteins, such as the soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor (SNARE) proteins for docking both membranes, and is integral to neurotransmission. (elsevierpure.com)
  • In contrast, it was found that decreases in SNARE proteins, except for SNAP-25, were not observed in vitamin E-supplemented rats, even when the rats were subjected to oxidative stress. (elsevierpure.com)
  • Neuronal ceroid lipofuscinosis with DNAJC5/CSPalpha mutation has PPT1 pathology and exhibit aberrant protein palmitoylation. (medlineplus.gov)
  • Other areas of interest include the development of molecular technologies for imaging and manipulation of neuronal gene expression, integration and analysis of molecular datasets, extracellular vesicles, nuclear architecture, nucleosynaptic communication and intergenerational inheritance. (nih.gov)
  • Vesicle acidification causes a conformational change in the toxin, allowing its HC part to function as a channel through which its LC part is extruded into the neuronal cytosol. (reactome.org)
  • In addition to mediating synaptic efficacy, BDNF also promotes differentiation, neurite (process) extension, and the survival of a variety of neuronal populations in culture and in vivo . (lww.com)
  • This illustration highlights spherical pre-synaptic vesicles that carry the neurotransmitter glutamate, and the pre-synaptic and post-synaptic membranes are shown with proteins relevant for transmitting and modulating the neuronal signal. (rcsb.org)
  • Alpha-synuclein is a small neuronal protein that is closely associated with the etiology of Parkinson's disease. (en-journal.org)
  • Glutamate is first synthesized in the cytoplasm of presynaptic terminals before being loaded into synaptic vesicles, which fuse with the plasma membrane, releasing their contents, in response to neuronal activity. (nih.gov)
  • Neurexins are a large family of proteins that act as neuronal cell-surface receptors. (johnshopkins.edu)
  • The aim of this study was to analyze the role of the genetic variants of two synaptic vesicle proteins (VAMP2 and Synaptotagmin XI) and two presynaptic plasma membrane proteins (Syntaxin 1A and SNAP-25) in patients with idiopathic generalized epilepsy (IGE). (nih.gov)
  • and BoNT/C also cleaves the plasma membrane protein syntaxin 1. (nature.com)
  • Similarly, marked decreases in the levels of SNAP-25 and syntaxin-1 in pre-synaptic plasma membranes were also observed. (elsevierpure.com)
  • The HC contains two sub-domains: the C-terminal H C that mediates binding to receptors, and the N-terminal H N that mediates translocation of the LC across endosomal membranes. (nature.com)
  • The macromolecules bind to receptors located in clathrin-coated pits in the plasma membrane. (tocris.com)
  • SynGAP is reported to inhibit synaptic accumulation of AMPA receptors. (nih.gov)
  • As a consequence, the transmitter illustrated by red triangles diffuses through the synaptic cleft to the postsynaptic receptors, which finally elicits an electrical signal in the postsynaptic cell. (hstalks.com)
  • Synaptic vesicle fusion is driven by the formation of a four-helical bundle composed of soluble N- ethylmaleimide sensitive factor (NSF) attachment protein receptors (SNAREs). (jneurosci.org)
  • Here, we focus on NMDA receptors (NMDARs) as proteins that could be modulating the association and neurotoxic perforation induced by Aβ on the plasma membrane. (marquette.edu)
  • Beta-neurexins are candidate receptors for neuroligin-1, a postsynaptic membrane protein that can trigger synapse formation at axon contacts. (johnshopkins.edu)
  • In spite of impressive progress made in the past years, not all known vesicular functions can be assigned to defined protein components, suggesting that the repertoire of synaptic vesicle proteins is still incomplete. (cornell.edu)
  • We have identified and characterized a novel synaptic vesicle membrane protein of 31 kDa with six putative transmembrane helices that, according to its membrane topology and phylogenetic relation, may function as a vesicular transporter. (cornell.edu)
  • The protein is expressed in select brain regions and contained in subpopulations of nerve terminals that immunostain for the vesicular glutamate transporter 1 and the vesicular GABA transporter VGaT (vesicular amino acid transporter) and may attribute specific and as yet undiscovered functions to subsets of glutamatergic and GABAergic synapses. (cornell.edu)
  • In particular, we find that vesicular glutamate transporter 1 (VGLUT1) recycles by two distinct endocytic pathways, which may in turn target to the different synaptic vesicle pools. (nih.gov)
  • In an ex vivo whole-brain preparation, fluorescent reporters of vesicular cargo and of vesicular pH reveal that amphetamine redistributes vesicle contents and diminishes the vesicle pH-gradient responsible for dopamine uptake and retention. (nih.gov)
  • The binding of calcium to the vesicular protein, synaptotagmin, is involved in triggering this fusion. (hstalks.com)
  • The important process of synaptic vesicle loading is mediated by a transport protein, collectively known as vesicular glutamate transporter (VGLUT). (nih.gov)
  • These advantages come at the cost of unwanted substrate interactions which can denature membrane proteins. (wikipedia.org)
  • The potential of mean force (PMF) between SYT and phospholipid bilayers is calculated using the adaptive biasing technique [7] and shows that Ca 2+ binding to SYT is required creates favorable protein bilayer interactions that lead to the insertion of SYT. (aiche.org)
  • Signalling at nerve cell synapses - a key determinant of all aspects of brain function - depends on hundreds of synaptic proteins and their interactions, and a wide range of neurological and psychiatric disorders are synapse disorders or 'synaptopathies', whose onset and progression are due to mutations of synaptic proteins and subsequent synaptic dysfunctions. (europa.eu)
  • However, it has been difficult to extend the study of precise molecular interactions among SNAREs to CNS synapses, where neurotransmitter is packaged in small, clear vesicles and transmitter release occurs on a faster time scale. (jneurosci.org)
  • Cross-linking mass spectrometry uncovers protein interactions and functional assemblies in synaptic vesicle membranes. (mpg.de)
  • Taken together, synaptotagmin appears to trigger a fast synchronous component of transmitter release by binding to Ca 2+ , probably through the interactions with both membranes and SNAREs. (elsevierpure.com)
  • These interactions are considered critical for at least some normal functions of alpha-synuclein, and may well play critical roles in both the aggregation of the protein and its mechanisms of toxicity. (en-journal.org)
  • Here we review the known features of alpha-synuclein membrane interactions in the context of both the putative functions of the protein and of its pathological roles in disease. (en-journal.org)
  • Oligomerization of neuroligin is required for its function, and we find that beta-neurexin clustering is sufficient to trigger the recruitment of synaptic vesicles through interactions that require the cytoplasmic domain of neurexin. (johnshopkins.edu)
  • Fig. 2: Domain structure and protein interactions of intersectin 1L (ITSN1-L) (taken from Pechstein et al. (sfb958.de)
  • this involves the uptake of molecules into non-clathrin coated membrane pits, known as caveolae. (tocris.com)
  • 2016 ) Distinct modes of endocytotic presynaptic membrane and protein uptake at the calyx of Held terminal of rats and mice. (neurotree.org)
  • Glutamate uptake into synaptic vesicles is regulated by intraneuronal availability of glutamate, gradient of H + -ions, and the intraluminal chloride ion concentration (see Figure 2). (sysy.com)
  • This figure illustrates the potential regulation of the glutamate uptake into the synaptic vesicles at the synapse. (sysy.com)
  • Neurotransmitter uptake of synaptic vesicles studied by X-ray diffraction. (mpg.de)
  • OBJECTIVE: The goal of this study was to determine the in vivo functions of the synaptic proteins neurexins and neuroligins in embryonic vascular system development using zebrafish as animal model. (inrae.fr)
  • The PSD core, extending up to 40 nm from the postsynaptic membrane, typically shows label for SynGAP, while half of the synapses exhibit additional labeling in a zone 40-120 nm from the postsynaptic membrane. (nih.gov)
  • We show that although synaptojanin is recruited by endophilin at bud necks before fission, the knockout of all three mouse endophilins results in the accumulation of clathrin-coated vesicles, but not of clathrin-coated pits, at synapses. (ox.ac.uk)
  • Midorikawa M, Sakaba T. ( 2017 ) Kinetics of Releasable Synaptic Vesicles and Their Plastic Changes at Hippocampal Mossy Fiber Synapses. (neurotree.org)
  • The release of neurotransmitter at synapses is regulated by proteins that form the presynaptic release machine. (eneuro.org)
  • Using some of these mouse lines as well as newly developed subcellular fractionation protocols, EUROSPIN partners have characterized key disease-relevant protein complexes of synapses and their protein components. (europa.eu)
  • VGLUT1 and VGLUT2, the two major isoforms of VGLUT in the brain, are expressed in two functionally-distinct subpopulations of glutamatergic synapses that differ in their probability of transmitter release and capacity for synaptic plasticity (Du et al. (sysy.com)
  • Neuroligins constitute a family of transmembrane proteins localized at the postsynaptic side of both excitatory and inhibitory synapses of the central nervous system. (inrae.fr)
  • Recent studies on VGLUT1-deficient mice have led various models to be postulated concerning the possible roles of VGLUTs in synaptic physiology, such as presynaptic regulation of quantal size and activity-dependent short-term plasticity. (nih.gov)
  • Stonin2 interacts with synaptotagmin to facilitate uncoating of clathrin-coated vesicles Ref:Walther, K., et al. (antibodiesinc.com)
  • Synaptotagmin (SYT) and SNAREs have been identified as critical proteins that regulate membrane fusion in concert with Ca 2+ [1, 2]. (aiche.org)
  • Synaptotagmin is a synaptic vesicle membrane protein that is postulated to function as a calcium (Ca 2+ ) sensor for neurotransmitter release. (elsevierpure.com)
  • In vitro studies demonstrate that synaptotagmin binds to phospholipid membranes in the presence and absence of Ca 2+ . (elsevierpure.com)
  • Furthermore, in response to Ca 2+ , the tips of synaptotagmin C2 domains penetrate lipid bilayers, altering the membrane curvature. (elsevierpure.com)
  • Its discovery posts a challenge to develop effective countermeasures, provides a novel tool for studying intracellular membrane trafficking, and presents a new potential therapeutic toxin for modulating secretions in cells. (nature.com)
  • The plasma membrane surrounds the particles forming a vesicle, which detaches from the plasma membrane and is trafficked to its intracellular destination. (tocris.com)
  • The main histopathological markers are the senile plaques formed by amyloid-β peptide (Aβ) aggregates that can perforate the plasma membrane of cells, increasing the intracellular calcium levels and releasing synaptic vesicles that finally lead to a delayed synaptic failure. (marquette.edu)
  • We find that the major source of membrane is intracellular, rather than in the form of a plasma membrane reservoir. (rupress.org)
  • Similar to BoNT/B/D/F/G, BoNT/X cleaves vesicle-associated membrane proteins (VAMP) 1, 2 and 3, but at a novel site (Arg66-Ala67 in VAMP2). (nature.com)
  • Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. (nih.gov)
  • The encoded protein is involved in the fusion of synaptic vesicles with the presynaptic membrane. (nih.gov)
  • SYT, a C2-domain family protein is thought to act as a Ca 2+ sensor, although there is still debate as to the precise mechanism through which SYT enhances membrane fusion. (aiche.org)
  • In one hypothesis, SYT penetrates the negatively charged membrane bilayer after binding Ca 2+ , causing tubulation of the bilayer, thereby lowering the activation energy barrier for fusion [3]. (aiche.org)
  • The primary role of SNAREs is in bridging the apposed synaptic vesicle and plasma membrane, by forming a core fusion complex. (aiche.org)
  • Upon the arrival of an action potential in the presynaptic terminal illustrated by the red arrow, voltage-dependent calcium channels open, and the influx of calcium triggers the fusion of transmitter-filled synaptic vesicles. (hstalks.com)
  • Release of neurotransmitter requires the fusion of synaptic vesicles with the presynaptic plasma membrane. (jneurosci.org)
  • Communication within the nervous system involves the exocytic fusion of neurotransmitter-filled synaptic vesicles (SVs), neurosecreÂ-tory organelles that comprise distinct sets of proteins and lipids, at active zone membranes. (sfb958.de)
  • Many different cell types show a polarized organization reflected in the asymmetric distribution of proteins and lipids in the plasma membrane and the asymmetric organization of the microtubule and actin cytoskeleton. (rupress.org)
  • Although it is known that cytosolic/soluble proteins synthesized in cell bodies are transported at much lower overall velocities than vesicles in fast axonal transport, the fundamental basis for this slow movement is unknown. (jneurosci.org)
  • Our studies uncover the underlying kinetic basis for a classic cytosolic/soluble protein moving in slow axonal transport and reveal previously unknown links between slow and fast transport, offering a clearer conceptual picture of this curious phenomenon. (jneurosci.org)
  • Despite this compositional diversity, the overall movement of diverse cytosolic/soluble/SCb proteins seems surprisingly cohesive ( Garner and Lasek, 1982 ). (jneurosci.org)
  • Although alpha-synuclein is a highly soluble, cytoplasmic protein, it binds to a variety of cellular membranes of different properties and compositions. (en-journal.org)
  • Using a standardized procedure to produce soluble aggregates of these three proteins, researchers led by Dominic Walsh, Brigham and Women's Hospital, Boston, report that all three types of aggregate bind to the same sequence in cellular prion protein (PrPC). (alzforum.org)
  • The new findings by Walsh and colleagues support the role of PrP as a 'general receptor' of soluble protein aggregates," wrote Thal and Luis Gomes, also from KU Leuven, in a comment to Alzforum (see below). (alzforum.org)
  • This is partly because, until now, there was no standardized procedure for preparing soluble protein aggregates, Walsh explained. (alzforum.org)
  • First author Grant Corbett and colleagues developed a reproducible procedure to generate homogenous soluble protein aggregates of Aβ, tau, and α-synuclein. (alzforum.org)
  • Aβ, tau, and α-synuclein monomers were not toxic to these cells, but soluble aggregates of all three proteins stunted neurites in both. (alzforum.org)
  • Author Correction: Isolation of large dense-core vesicles from bovine adrenal medulla for functional studies. (mpg.de)
  • The botulinum neurotoxin serotypes cleave the peptide bonds at specific sites on the 3 proteins, as indicated. (cdc.gov)
  • This resulted in a first visualization of overall protein motion in the synapse, which should enable future modeling studies of synaptic physiology. (units.it)
  • Moreover, relatively little is known regarding the regulation of clathrin-mediated budding at other membrane systems. (rupress.org)
  • Stonin 2 is membrane bound protein that is involved in the regulation of endocytotic complexes and synaptic vesicle recycling. (antibodiesinc.com)
  • This protein is found near nerve cells in the brain, where it plays a role in the transmission of nerve impulses. (medlineplus.gov)
  • CSPα is involved in recycling proteins that are involved in nerve impulse transmission by re-folding misshapen proteins so that they can be used in additional transmissions. (medlineplus.gov)
  • The resulting reduction in protein recycling leads to a shortage (deficiency) of functional proteins, which impairs the efficiency of nerve impulse transmission. (medlineplus.gov)
  • The abnormal CSPα protein may also bind to the functional CSPα protein that is produced from the normal copy of the DNAJC5 gene and prevent it from associating with synaptic vesicles, further impairing impulse transmission. (medlineplus.gov)
  • Cleavage of any 1 of these proteins prevents vesicle membrane docking and nerve impulse transmission. (cdc.gov)
  • The absence of endophilin impairs but does not abolish synaptic transmission and results in perinatal lethality, whereas partial endophilin absence causes severe neurological defects, including epilepsy and neurodegeneration. (ox.ac.uk)
  • Many proteins involved in synaptic transmission are well known, and their features, as their abundance or spatial distribution, have been analyzed in systematic studies. (units.it)
  • To address this question, we used a strategy to "rescue" synaptic transmission after proteolytic cleavage of the synaptosome-associated protein of 25 kDa (SNAP-25) by botulinum neurotoxin E (BoNtE). (jneurosci.org)
  • Transfection of CA3 hippocampal pyramidal cells with BoNtE-resistant SNAP-25 restored synaptic transmission. (jneurosci.org)
  • Following receptor binding, adaptor proteins in the cell cytoplasm recruit clathrin chains, which polymerize forming invaginations in the plasma membrane. (tocris.com)
  • The adaptor complex AP-2 is the major clathrin-associated adaptor for cargo recognition at the plasma membrane. (cornell.edu)
  • Activity-induced movement of SynGAP could vacate sites in the PSD core allowing other elements to bind to these sites, such as transmembrane AMPA receptor regulatory proteins (TARPs), and simultaneously facilitate access of SynGAP to CaMKII and Ras, elements of a regulatory cascade. (nih.gov)
  • Glucagon exerts activity through G protein coupled receptor systems. (pharmacology2000.com)
  • Nox4 was required for the expression of uncoupling protein 3 (Ucp3), hexokinase 2 (Hk2), and pyruvate dehydrogenase kinase 4 (Pdk4), but not the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1α). (bvsalud.org)
  • The Level of NMDA Receptor in the Membrane Modulates Amyloid-β Associa" by Christian Peters, Fernando J. Sepúlveda et al. (marquette.edu)
  • The DNAJC5 gene provides instructions for making a protein called cysteine string protein alpha (CSPα). (medlineplus.gov)
  • One of the DNAJC5 gene mutations replaces the protein building block (amino acid) leucine with the amino acid arginine at position 115 in the CSPα protein (written as L115R). (medlineplus.gov)
  • Affected individuals have one of these mutations in one copy of the DNAJC5 gene in each cell, which leads to the production of an altered protein that cannot associate with the membrane of synaptic vesicles. (medlineplus.gov)
  • Because of its high homology to other known VAMPs, its broad tissue distribution, and its subcellular localization, the protein encoded by this gene was shown to be the human equivalent of the rodent cellubrevin. (nih.gov)
  • Description of the protein which includes the UniProt Function and the NCBI Gene Summary. (nih.gov)
  • Studies on disease-relevant gene products concentrated on a very wide array of proteins. (europa.eu)
  • On aggregate, EUROSPIN work on a large number of disease gene products has yielded a wealth of insights into the mechanism by which the respective mutation or loss of such proteins might cause disease phenotypes. (europa.eu)
  • We report the cloning of a zebrafish paired-type homeobox gene, Alx, closely related to the murine Chx10 and the gold fish Vsx-I homeodomain proteins. (inrae.fr)
  • In platelets the protein resides on a compartment that is not mobilized to the plasma membrane on calcium or thrombin stimulation. (nih.gov)
  • Despite numerous advances in the identification of the molecular machinery for clathrin-mediated budding at the plasma membrane, the mechanistic details of this process remain incomplete. (rupress.org)
  • Amphetamine-induced vesicle deacidification also requires functional dopamine transporter (DAT) at the plasma membrane. (nih.gov)
  • Increased cAMP enhances protein kinase A catalytic activity thus activating phosphorylase leading to glycogen breakdown and an increase in plasma glucose. (pharmacology2000.com)
  • The enlargement shows the double lipid membrane of the vesicle and the presynaptic plasma membrane. (hstalks.com)
  • In contrast, the organization of the proteins at the presynaptic plasma membrane that built the active zone is less well understood. (hstalks.com)
  • Depolymerization of microtubules inhibits the export of a newly synthesized transmembrane protein from the Golgi apparatus to the plasma membrane and simultaneously blocks membrane growth. (rupress.org)
  • The EUROSPIN consortium was initiated with the aim of pursuing a multilevel systems biology approach to determine mechanistic relationships between mutations of synaptic proteins and neurological and psychiatric diseases, and to develop new diagnostic tools and therapies. (europa.eu)
  • They are involved in synaptic function and maturation and recent studies have linked mutations in specific human Neuroligins to mental retardation and autism. (inrae.fr)
  • CLN4 disease is characterized by the accumulation of proteins and other substances in lysosomes, which are compartments in the cell that digest and recycle materials. (medlineplus.gov)
  • These proteins aggregate at presynaptic active zones (AZs) to form the cytomatrix at the active zone (CAZ), which controls the recruitment, docking, and priming of synaptic vesicles and enhances calcium channel accumulation ( Gundelfinger and Fejtova, 2012 ). (eneuro.org)
  • Transcytosis and trans-synaptic retention by postsynaptic ErbB4 underlie axonal accumulation of NRG3. (nih.gov)
  • SynGAP is a Ras GTPase activating protein present at the postsynaptic density (PSD) in quantities matching those of the core scaffold protein PSD-95. (nih.gov)
  • Endophilin also binds the GTPase dynamin and the phosphoinositide phosphatase synaptojanin and is thought to coordinate constriction of coated pits with membrane fission (via dynamin) and subsequent uncoating (via synaptojanin). (ox.ac.uk)
  • At the Drosophila neuromuscular junction (NMJ), the small GTPase Rab3 controls the distribution of CAZ proteins across release sites, thereby regulating the efficacy of individual AZs. (eneuro.org)
  • All glutamate transporters (EAATs and VGLUTs) are multispanning membrane proteins with up to 12 transmembrane domains. (sysy.com)
  • The translocation of glutamate into synaptic vesicles by VGLUTs depends on a proton gradient that is established by a V-Type H + -ATPase. (sysy.com)
  • The influx of protons into the vesicle causes a drop in intraluminal pH and a change in membrane potential, driving the transport of glutamate. (sysy.com)
  • Glutamate is pumped into the vesicle together with a monovalent cation (preferable K + , but also e.g. (sysy.com)
  • They start transporting glutamate into the vesicle and chloride ions out of the vesicle. (sysy.com)
  • Step 3: More and more glutamate and H + are incorporated into the vesicle, and the higher concentration of H + causes the intraluminal pH to decrease more and more. (sysy.com)
  • Step 4: The vesicles are now filled with glutamate and have lost nearly all of the chloride ions. (sysy.com)
  • This lack of intraluminal chloride ions is assumed to eliminate the allosteric activation of the VGLUTs by influencing the conductance, preventing so an "over-filling" of the vesicles with glutamate. (sysy.com)
  • Although the difference between these pools is often considered to reflect differences in their history, or association with cytoskeletal proteins, work on the recycling of a specific synaptic vesicle protein now suggests that the pools may differ in their molecular components. (nih.gov)
  • The role that transcription factors, non-coding RNAs, scaffolding proteins, adhesion molecules, signaling molecules, cytoskeletal proteins, and other molecules play in mediating memory and learning and the neural adaptation to addictive drugs. (nih.gov)
  • Similar repeat sequences are found in the exchangeable apolipoproteins, and as for many apolipoproteins, the N-terminal lipid-binding domain of alpha synuclein adopts an amphipathic helical structure upon binding to detergent micelles or phospholipid vesicles. (en-journal.org)
  • Synaptic vesicles appear very homogeneous, and within a particular nerve terminal, they are generally presumed to contain the same set of integral membrane proteins. (nih.gov)
  • Additional research showed that resulting protein inactivation disrupted nerve terminal processes and impaired neurotransmission. (nih.gov)
  • Such spatio-temporal control of the SV cycle within the nerve terminal likely involves membrane-associated multidomain scaffolds including intersectin (5) (Figure 2) and Eps15. (sfb958.de)
  • GPCRs can interact with multiple distinct transducers or regulatory proteins and these can be preferentially engaged in an agonist-specific manner giving rise to biased agonism. (tocris.com)
  • Despite the distinct overall dynamics of slow and fast transport, experimentally induced and intrinsic variations in vesicle transport have analogous effects on slow transport of synapsin as well. (jneurosci.org)
  • It is also unclear whether membrane growth and polarization represent distinct processes that occur simultaneously or whether growth of the membrane is involved in the emergence of polarity. (rupress.org)
  • Synaptic signaling involves the release of neurotransmitter from presynaptic active zones (AZs). (eneuro.org)
  • Clathrin-based SV recycling in addition to clathrin (2) involves endocytic adaptors such as stonin 2 (3) and AP180 (4) as well as accessory proteins that contribute to SV cargo sorting, membrane deformation, remodelling, and fission. (sfb958.de)
  • To identify new candidate CA proteins, we used mass spectrometry to compare axonemes of wild-type Chlamydomonas and a CA-less mutant. (bvsalud.org)
  • Indeed, this was one of the first clues that this technique produced a membrane of molecular-scale thickness. (wikipedia.org)
  • Our studies reveal that Rab3 and Rab3-GEF act within the same molecular mechanism and support a model wherein Rab3-GEF serves as a Rab3 effector to control active zone protein composition. (eneuro.org)
  • Although subÂ-stantial progress has been made towards unravelling the mechanics of CME, the spatio-temporal dynamics of endocytic proteins within the endocytic or periactive zone and the underlying molecular mechanisms have remained elusive. (sfb958.de)
  • they include design of new fluorescence instruments, protein dynamics, hydration of proteins, and I.R. spectroscopy of biological substances. (fluorescence-foundation.org)
  • [ 30-32 ] Once exposed to physiological pH in the tissues of the neuromuscular junction, the neurotoxin, which is identical in each product, dissociates from the proteins and acts on the presynaptic terminal. (medscape.com)
  • Functional studies of RIMS3 variants such as p.E177A should provide additional insight into the role of synaptic proteins in the pathophysiology of autism. (nih.gov)
  • However, considerable work has demonstrated that synaptic vesicles differ dramatically in their functional properties. (nih.gov)
  • Dynamic cotransport of vesicles and synapsin particles is also seen in axons, consistent with a model where higher-order assemblies of synapsin are conveyed by transient and probabilistic associations with vesicles moving in fast axonal transport. (jneurosci.org)
  • Using a combination of surface labeling and particles tracking techniques, we monitored the dynamics of marked membrane regions during cellularization. (rupress.org)
  • The function of these proteins has not been clearly delineated, but some studies indicate that they stabilize the structural integrity of the compound in an acidic environment such as the gastrointestinal tract, thereby protecting the toxin as it passes through the stomach until it reaches the small intestine where it can be absorbed. (medscape.com)
  • Both onabotulinumtoxinA and abobotulinumtoxinA are associated with complexing proteins in differing amounts, whereas incobotulinumtoxinA, the newest formulation on the market, is pure toxin with the proteins removed. (medscape.com)
  • Functionally, the reduction in membrane NMDARs augmented the process of membrane perforation. (marquette.edu)