Neurotransmitter release mechanisms and microtubules

1983 ◽  
Vol 218 (1211) ◽  
pp. 253-258 ◽  
Keyword(s):  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Ordered Structure ◽  
Presynaptic Membrane ◽  
Vesicle Membrane ◽  
Ordered Arrays ◽  
The Central Nervous System ◽  
Active Zones ◽  
Dense Projections ◽  
Regular Arrays

The morphological mechanisms involved in translocation of the synaptic vesicle to the presynaptic membrane, release of transmitter from the vesicle and recycling of the vesicle membrane are still far from understood. However, there is strong evidence that vesicles move along the surfaces of a specific set of highly labile presynaptic microtubules that direct the vesicles to the active zones. These microtubules are focused in a precise geometrical array, which is in register with and in contact with presynaptic dense projections of the central nervous system synapse or presynaptic dense bars of the motor endplate. These dense complexes constitute the presynaptic grid or active zones. The regular arrays of dense projections or bars are in turn coincident with rings or chains of synaptic vesicles mobilized at release sites on the presynaptic membrane (having arrived at these precise points by microtubule translocation). Thus it is suggested that the presynaptic microtubules not only translocate synaptic vesicles, but because of their ordered arrays determine, in ontogeny, the ordered structure of the presynaptic grid.

scholarly journals Synaptic Vesicles Having Large Contact Areas with the Presynaptic Membrane are Preferentially Hemifused at Active Zones of Frog Neuromuscular Junctions Fixed during Synaptic Activity

2019 ◽  
Vol 20 (11) ◽  
pp. 2692
Author(s):  
Jae Hoon Jung
Keyword(s):  
Synaptic Vesicles ◽  
Neuromuscular Junctions ◽  
Synaptic Activity ◽  
Membrane Thickness ◽  
Intermediate Step ◽  
Presynaptic Membrane ◽  
Vesicle Membrane ◽  
Contact Areas ◽  
Contact Sites ◽  
Active Zones

Synaptic vesicles dock on the presynaptic plasma membrane of axon terminals and become ready to fuse with the presynaptic membrane or primed. Fusion of the vesicle membrane and presynaptic membrane results in the formation of a pore between the membranes, through which the vesicle’s neurotransmitter is released into the synaptic cleft. A recent electron tomography study on frog neuromuscular junctions fixed at rest showed that there is no discernible gap between or merging of the membrane of docked synaptic vesicles with the presynaptic membrane, however, the extent of the contact area between the membrane of docked synaptic vesicles and the presynaptic membrane varies 10-fold with a normal distribution. The study also showed that when the neuromuscular junctions are fixed during repetitive electrical nerve stimulation, the portion of large contact areas in the distribution is reduced compared to the portion of small contact areas, suggesting that docked synaptic vesicles with the largest contact areas are greatly primed to fuse with the membrane. Furthermore, the finding of several hemifused synaptic vesicles among the docked vesicles was briefly reported. Here, the spatial relationship of 81 synaptic vesicles with the presynaptic membrane at active zones of the neuromuscular junctions fixed during stimulation is described in detail. For the most of the vesicles, the combined thickness of each of their contact sites was not different from the sum of the membrane thicknesses of the vesicle membrane and presynaptic membrane, similar to the docked vesicles at active zones of the resting neuromuscular junctions. However, the combined membrane thickness of a small portion of the vesicles was considerably less than the sum of the membrane thicknesses, indicating that the membranes at their contact sites were fixed in a state of hemifusion. Moreover, the hemifused vesicles were found to have large contact areas with the presynaptic membrane. These findings support the recently proposed hypothesis that, at frog neuromuscular junctions, docked synaptic vesicles with the largest contact areas are most primed for fusion with the presynaptic membrane, and that hemifusion is a fusion intermediate step of the vesicle membrane with the presynaptic membrane for synaptic transmission.

scholarly journals Botulinum Neurotoxin a Blocks Synaptic Vesicle Exocytosis but Not Endocytosis at the Nerve Terminal

1999 ◽  
Vol 147 (6) ◽  
pp. 1249-1260 ◽  
Author(s):  
Elaine A. Neale ◽  
Linda M. Bowers ◽  
Min Jia ◽  
Karen E. Bateman ◽  
Lura C. Williamson
Keyword(s):  
Synaptic Vesicle ◽  
Nerve Terminal ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Botulinum Neurotoxin ◽  
Vesicle Membrane ◽  
Botulinum Neurotoxin A ◽  
Synaptic Vesicle Exocytosis ◽  
Vesicle Exocytosis ◽  
Botulinum Neurotoxins

The supply of synaptic vesicles in the nerve terminal is maintained by a temporally linked balance of exo- and endocytosis. Tetanus and botulinum neurotoxins block neurotransmitter release by the enzymatic cleavage of proteins identified as critical for synaptic vesicle exocytosis. We show here that botulinum neurotoxin A is unique in that the toxin-induced block in exocytosis does not arrest vesicle membrane endocytosis. In the murine spinal cord, cell cultures exposed to botulinum neurotoxin A, neither K+-evoked neurotransmitter release nor synaptic currents can be detected, twice the ordinary number of synaptic vesicles are docked at the synaptic active zone, and its protein substrate is cleaved, which is similar to observations with tetanus and other botulinal neurotoxins. In marked contrast, K+ depolarization, in the presence of Ca2+, triggers the endocytosis of the vesicle membrane in botulinum neurotoxin A–blocked cultures as evidenced by FM1-43 staining of synaptic terminals and uptake of HRP into synaptic vesicles. These experiments are the first demonstration that botulinum neurotoxin A uncouples vesicle exo- from endocytosis, and provide evidence that Ca2+ is required for synaptic vesicle membrane retrieval.

scholarly journals Vesicle-associated membrane protein-2 (synaptobrevin-2) forms a complex with synaptophysin

1995 ◽  
Vol 305 (3) ◽  
pp. 721-724 ◽  
Author(s):  
P Washbourne ◽  
G Schiavo ◽  
C Montecucco
Keyword(s):  
Membrane Protein ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Cross Linking ◽  
Type Ii ◽  
Presynaptic Membrane ◽  
Terminal Part ◽  
Vesicle Docking ◽  
Botulinum Neurotoxins ◽  
Type Ii Membrane Protein

Vesicle-associated membrane protein (VAMP) (or synaptobrevin), a type II membrane protein of small synaptic vesicles, is essential for neuroexocytosis because its proteolysis by tetanus and botulinum neurotoxins types B, D, F and G blocks neurotransmitter release. The addition of cross-linking reagents to isolated small synaptic vesicles induces the formation of 30 and 50 kDa complexes containing the isoform 2 of VAMP (VAMP-2). Whereas the 30 kDa band is a VAMP-2 homodimer, the 50 kDa species results from the cross-linking of VAMP-2 with synaptophysin. This heterodimer also forms in detergent-solubilized vesicles and involves the N-terminal part of VAMP-2. The implications of the existence of a synaptophysin-VAMP-2 complex in the processes of vesicle docking and fusion with the presynaptic membrane are discussed.

scholarly journals Protein–protein interactions and protein modules in the control of neurotransmitter release

1999 ◽  
Vol 354 (1381) ◽  
pp. 243-257 ◽  
Author(s):  
Fabio Benfenati ◽  
Franco Onofri ◽  
Silvia Giovedí
Keyword(s):  
Synaptic Vesicle ◽  
Protein Interactions ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Physiological Role ◽  
Presynaptic Membrane ◽  
Protein Protein Interactions ◽  
Sequence Of Events ◽  
Reserve Pool ◽  
Protein Modules

Information transfer among neurons is operated by neurotransmitters stored in synaptic vesicles and released to the extracellular space by an efficient process of regulated exocytosis. Synaptic vesicles are organized into two distinct functional pools, a large reserve pool in which vesicles are restrained by the actin–based cytoskeleton, and a quantitatively smaller releasable pool in which vesicles approach the presynaptic membrane and eventually fuse with it on stimulation. Both synaptic vesicle trafficking and neurotransmitter release depend on a precise sequence of events that include release from the reserve pool, targeting to the active zone, docking, priming, fusion and endocytotic retrieval of synaptic vesicles. These steps are mediated by a series of specific interactions among cytoskeletal, synaptic vesicle, presynaptic membrane and cytosolic proteins that, by acting in concert, promote the spatial and temporal regulation of the exocytotic machinery. The majority of these interactions are mediated by specific protein modules and domains that are found in many proteins and are involved in numerous intracellular processes. In this paper, the possible physiological role of these multiple protein–protein interactions is analysed, with ensuing updating and clarification of the present molecular model of the process of neurotransmitter release.

scholarly journals Freeze-fracture studies of frog neuromuscular junctions during intense release of neurotransmitter. III. A morphometric analysis of the number and diameter of intramembrane particles.

1980 ◽  
Vol 85 (2) ◽  
pp. 337-345 ◽  
Author(s):  
R Fesce ◽  
F Grohovaz ◽  
W P Hurlbut ◽  
B Ceccarelli
Keyword(s):  
Synaptic Vesicles ◽  
Neuromuscular Junctions ◽  
Freeze Fracture ◽  
Presynaptic Membrane ◽  
Small Particles ◽  
Vesicle Membrane ◽  
Intramembrane Particles ◽  
Large Particles ◽  
Black Widow Spider Venom ◽  
Indirect Stimulation

The intramembrane particles on the presynaptic membrane and on the membrane of synaptic vesicles were studied at freeze-fractured neuromuscular junctions of the frog. The particles on the P face of the presynaptic membrane belong to two major classes: small particles with diameters less than 9 nm and large particles with diameters between 9 and 13 nm. In addition, there were a few extralarge particles with diameters greater than 13 nm. Indirect stimulation of the muscle, or the application of black widow spider venom, decreased the concentration of small particles on the presynaptic membrane but did not change the concentration of large particles. Three similar classes of particles were found on the P face of the membrane of the synaptic vesicles. The concentrations of large and extralarge particles on the vesicle membrane were comparable to the concentrations of these particles on the presynaptic membrane, whereas the concentration of small particles on the vesicle membrane was less than than the concentration of small particles on the presynaptic membrane. These results are compatible with the idea that synaptic vesicles fuse with the presynaptic membrane when quanta of transmitter are released. However, neither the large nor the extralarge particles on the P face of the presynaptic membrane can be used to trace the movement of vesicle membrane that has been incorporated into the axolemma.

Macroporous Materials with Uniform Pores by Emulsion Templating

1997 ◽  
Vol 497 ◽  
Author(s):  
A. Imhof ◽  
D. J. Pine
Keyword(s):  
Colloidal Crystal ◽  
Sol Gel ◽  
Ordered Structure ◽  
Left Behind ◽  
Ordered Arrays ◽  
Emulsion Droplets ◽  
Sol Gel Process ◽  
Uniform Droplets ◽  
Emulsion Templating ◽  
Regular Arrays

ABSTRACTA method was developed for the production of macroporous oxide materials by using the droplets of a nonaqueous emulsion as the templates around which material is deposited through a sol-gel process. Moreover, uniform pores arranged in regular arrays can be obtained by starting with an emulsion of uniform droplets. These droplets first self-assemble into a colloidal crystal after which gelation of the suspending sol-gel mixture captures the ordered structure. After drying and calcination pellets are obtained which contain ordered arrays of spherical pores left behind by the emulsion droplets. The method can be used to make uniform pores in the range from 0.05–5 micrometers in many different materials. We demonstrate the process for titania, silica, and zirconia.

Protonation states at different pH, Conformational Changes and Impact of Glycosylation in Synapsin Ia

2021 ◽  
Author(s):  
Sonia Mir ◽  
Maria Saeed ◽  
Sajda Ashraf ◽  
Atta-ur Rahman ◽  
Zaheer Ul-Haq
Keyword(s):  
Neurite Outgrowth ◽  
Conformational Changes ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Synapsin I ◽  
Presynaptic Terminals ◽  
Active Zones

Synapsin I is the most abundant brain phosphoprotein present at presynaptic terminals which regulates neurotransmitter release, clustering of synaptic vesicles (SVs) at active zones, and stimulates synaptogenesis and neurite outgrowth....

Dendro-dendritic and reciprocal synapses in the primate motor cortex

1978 ◽  
Vol 203 (1150) ◽  
pp. 23-38 ◽  
Keyword(s):  
Motor Cortex ◽  
Synaptic Vesicles ◽  
Postsynaptic Membrane ◽  
Presynaptic Membrane ◽  
Membrane Specialization ◽  
Single Axon ◽  
Deep Layers ◽  
Presynaptic Dendrites ◽  
Symmetrical Type ◽  
Dense Projections

Dendro-dendritic synapses have been observed infrequently in the deep layers of the motor cortex. The presynaptic dendrites are of a varicose type and themselves receive a considerable density of synapses both of the asymmetric and symmetrical type. The ultrastructure of the dendro-dendritic synapse itself shows the typical arrangement of presynaptic and postsynaptic membrane densities, often with presynaptic dense projections, and the membrane specialization is of the symmetrical type. There is the usual cleft containing electron-dense material between the presynaptic and postsynaptic profiles. The synaptic vesicles occur in a small cluster confined to a region close to the presynaptic membrane specialization; some of the vesicles are flattened and were shown by tilt analysis to be of the discoid type. Two examples were found of reciprocal dendro-dendritic synapses, both components being of the symmetrical type. A single axon terminal may make a synapse on to both dendrites involved in a dendro-dendritic synapse.

Synaptic vesicles and microtubules in frog motor endplates

1978 ◽  
Vol 203 (1152) ◽  
pp. 219-227 ◽  
Keyword(s):  
Electron Microscopy ◽  
Skeletal Muscle ◽  
Small Proportion ◽  
Active Zone ◽  
Synaptic Vesicles ◽  
Presynaptic Membrane ◽  
Albumin Solution ◽  
Motor Endplates ◽  
Active Zones ◽  
A New Technique

Motor endplates of the cutaneous pectoris skeletal muscle of the frog have been examined by electron microscopy using a new technique. This involves pretreatment with an albumin solution, followed by fixation with 4% unbuffered tetroxide. A small proportion of the endplate axonal ramifications show microtubules clothed in synaptic vesicles and focused on the presynaptic membrane, in particular on the active zones. The microtubules run in the presynaptic cytoplasm either parallel to or across the active zones. These two sets of microtubules cross each other at the active zones, which lie opposite the dips in the post-junctional folds. The possibility that the microtubules are involved in the translocation of synaptic vesicles to the active zone is discussed.

scholarly journals The structure and function of ‘active zone material’ at synapses

2015 ◽  
Vol 370 (1672) ◽  
pp. 20140189 ◽  
Author(s):  
Joseph A. Szule ◽  
Jae Hoon Jung ◽  
Uel J. McMahan
Keyword(s):  
Spatial Resolution ◽  
Active Zone ◽  
Synaptic Vesicles ◽  
Neuromuscular Junctions ◽  
Electron Tomography ◽  
Structure And Function ◽  
Presynaptic Membrane ◽  
Axon Terminals ◽  
Active Zones ◽  
And Function

The docking of synaptic vesicles on the presynaptic membrane and their priming for fusion with it to mediate synaptic transmission of nerve impulses typically occur at structurally specialized regions on the membrane called active zones. Stable components of active zones include aggregates of macromolecules, ‘active zone material’ (AZM), attached to the presynaptic membrane, and aggregates of Ca 2+ -channels in the membrane, through which Ca 2+ enters the cytosol to trigger impulse-evoked vesicle fusion with the presynaptic membrane by interacting with Ca 2+ -sensors on the vesicles. This laboratory has used electron tomography to study, at macromolecular spatial resolution, the structure and function of AZM at the simply arranged active zones of axon terminals at frog neuromuscular junctions. The results support the conclusion that AZM directs the docking and priming of synaptic vesicles and essential positioning of Ca 2+ -channels relative to the vesicles' Ca 2+ -sensors. Here we review the findings and comment on their applicability to understanding mechanisms of docking, priming and Ca 2+ -triggering at other synapses, where the arrangement of active zone components differs.

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