Active zone assembly and synaptic release

2006 ◽  
Vol 34 (5) ◽  
pp. 939-941 ◽  
Author(s):  
R.J. Kittel ◽  
S. Hallermann ◽  
S. Thomsen ◽  
C. Wichmann ◽  
S.J. Sigrist ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Active Zone ◽  
Synaptic Vesicles ◽  
Spatial Arrangement ◽  
Transmission Characteristics ◽  
Vesicle Release ◽  
Synaptic Release ◽  
Voltage Gated Calcium Channels ◽  
Presynaptic Calcium ◽  
Chemical Synapses

Neurotransmitter release at chemical synapses occurs when synaptic vesicles fuse to the presynaptic membrane at a specialized site termed the active zone. The depolarization-induced fusion is highly dependent on calcium ions, and, correspondingly, the transmission characteristics of synapses are thought to be influenced by the spatial arrangement of voltage-gated calcium channels with respect to vesicle release sites. Here, we review the involvement of the Drosophila Bruchpilot (BRP) protein in active zone assembly, a process that is required for the clustering of presynaptic calcium channels to ensure efficient vesicle release.

scholarly journals Proteolytic maturation of α2δ controls the probability of synaptic vesicular release

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Laurent Ferron ◽  
Ivan Kadurin ◽  
Annette C Dolphin
Keyword(s):  
Calcium Channels ◽  
Inhibitory Effect ◽  
Wild Type ◽  
Voltage Gated ◽  
Synaptic Release ◽  
Voltage Gated Calcium Channels ◽  
Vesicular Release ◽  
Active Zones ◽  
Asynchronous Release

Auxiliary α2δ subunits are important proteins for trafficking of voltage-gated calcium channels (CaV) at the active zones of synapses. We have previously shown that the post-translational proteolytic cleavage of α2δ is essential for their modulatory effects on the trafficking of N-type (CaV2.2) calcium channels (Kadurin et al., 2016). We extend these results here by showing that the probability of presynaptic vesicular release is reduced when an uncleaved α2δ is expressed in rat neurons and that this inhibitory effect is reversed when cleavage of α2δ is restored. We also show that asynchronous release is influenced by the maturation of α2δ−1, highlighting the role of CaV channels in this component of vesicular release. We present additional evidence that CaV2.2 co-immunoprecipitates preferentially with cleaved wild-type α2δ. Our data indicate that the proteolytic maturation increases the association of α2δ−1 with CaV channel complex and is essential for its function on synaptic release.

scholarly journals Clarinet (CLA-1), a novel active zone protein required for synaptic vesicle clustering and release

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Zhao Xuan ◽  
Laura Manning ◽  
Jessica Nelson ◽  
Janet E Richmond ◽  
Daniel A Colón-Ramos ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Active Zone ◽  
Synaptic Vesicles ◽  
Synaptic Depression ◽  
Genetic Screens ◽  
Zone Structure ◽  
Vesicle Release ◽  
C2 Domains ◽  
Specific Loss ◽  
Forward Genetic Screens

Active zone proteins cluster synaptic vesicles at presynaptic terminals and coordinate their release. In forward genetic screens, we isolated a novel Caenorhabditis elegans active zone gene, clarinet (cla-1). cla-1 mutants exhibit defects in synaptic vesicle clustering, active zone structure and synapse number. As a result, they have reduced spontaneous vesicle release and increased synaptic depression. cla-1 mutants show defects in vesicle distribution near the presynaptic dense projection, with fewer undocked vesicles contacting the dense projection and more docked vesicles at the plasma membrane. cla-1 encodes three isoforms containing common C-terminal PDZ and C2 domains with homology to vertebrate active zone proteins Piccolo and RIM. The C-termini of all isoforms localize to the active zone. Specific loss of the ~9000 amino acid long isoform results in vesicle clustering defects and increased synaptic depression. Our data indicate that specific isoforms of clarinet serve distinct functions, regulating synapse development, vesicle clustering and release.

scholarly journals Transmitter release is evoked with low probability predominately by calcium flux through single channel openings at the frog neuromuscular junction

2015 ◽  
Vol 113 (7) ◽  
pp. 2480-2489 ◽  
Author(s):  
Fujun Luo ◽  
Markus Dittrich ◽  
Soyoun Cho ◽  
Joel R. Stiles ◽  
Stephen D. Meriney
Keyword(s):  
Neuromuscular Junction ◽  
Calcium Channels ◽  
Calcium Channel ◽  
Calcium Ions ◽  
Transmitter Release ◽  
Synaptic Vesicles ◽  
Vesicle Fusion ◽  
Frog Neuromuscular Junction ◽  
Low Probability ◽  
Presynaptic Calcium

The quantitative relationship between presynaptic calcium influx and transmitter release critically depends on the spatial coupling of presynaptic calcium channels to synaptic vesicles. When there is a close association between calcium channels and synaptic vesicles, the flux through a single open calcium channel may be sufficient to trigger transmitter release. With increasing spatial distance, however, a larger number of open calcium channels might be required to contribute sufficient calcium ions to trigger vesicle fusion. Here we used a combination of pharmacological calcium channel block, high-resolution calcium imaging, postsynaptic recording, and 3D Monte Carlo reaction-diffusion simulations in the adult frog neuromuscular junction, to show that release of individual synaptic vesicles is predominately triggered by calcium ions entering the nerve terminal through the nearest open calcium channel. Furthermore, calcium ion flux through this channel has a low probability of triggering synaptic vesicle fusion (∼6%), even when multiple channels open in a single active zone. These mechanisms work to control the rare triggering of vesicle fusion in the frog neuromuscular junction from each of the tens of thousands of individual release sites at this large model synapse.

scholarly journals Activity-evoked and spontaneous opening of synaptic fusion pores

2019 ◽  
Vol 116 (34) ◽  
pp. 17039-17044 ◽  
Author(s):  
Dinara Bulgari ◽  
David L. Deitcher ◽  
Brigitte F. Schmidt ◽  
M. Alexandra Carpenter ◽  
Christopher Szent-Gyorgyi ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Active Zone ◽  
Transmitter Release ◽  
Synaptic Vesicles ◽  
Pain Perception ◽  
Fusion Pore ◽  
Synaptic Release ◽  
Pore Opening ◽  
Active Zones ◽  
Fusion Pores

Synaptic release of neuropeptides packaged in dense-core vesicles (DCVs) regulates synapses, circuits, and behaviors including feeding, sleeping, and pain perception. Here, synaptic DCV fusion pore openings are imaged without interference from cotransmitting small synaptic vesicles (SSVs) with the use of a fluorogen-activating protein (FAP). Activity-evoked kiss and run exocytosis opens synaptic DCV fusion pores away from active zones that readily conduct molecules larger than most native neuropeptides (i.e., molecular weight [MW] up to, at least, 4.5 kDa). Remarkably, these synaptic fusion pores also open spontaneously in the absence of stimulation and extracellular Ca2+. SNARE perturbations demonstrate different mechanisms for activity-evoked and spontaneous fusion pore openings with the latter sharing features of spontaneous small molecule transmitter release by active zone-associated SSVs. Fusion pore opening at resting synapses provides a mechanism for activity-independent peptidergic transmission.

Synaptic vesicle recruitment for release explored by Monte Carlo simulation at the crayfish neuromuscular junction

1999 ◽  
Vol 77 (9) ◽  
pp. 634-650 ◽  
Author(s):  
K M Kennedy ◽  
S T Piper ◽  
H L Atwood
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Neuromuscular Junction ◽  
Calcium Channels ◽  
Calcium Channel ◽  
Synaptic Vesicle ◽  
Active Zone ◽  
Synaptic Vesicles ◽  
Single Channel ◽  
Separation Distance

Neurotransmission at chemically transmitting synapses requires calcium-mediated fusion of synaptic vesicles with the presynaptic membrane. Utilizing ultrastructural information available for the crustacean excitatory neuromuscular junction, we developed a model that employs the Monte Carlo simulation technique to follow the entry and movement of Ca2+ ions at a presynaptic active zone, where synaptic vesicles are preferentially docked for release. The model includes interaction of Ca2+ with an intracellular buffer, and variable separation between calcium channels and vesicle-associated Ca2+-binding targets that react with Ca2+ to trigger vesicle fusion. The end point for vesicle recruitment for release was binding of four Ca2+ ions to the target controlling release. The results of the modeling experiments showed that intracellular structures that interfere with Ca2+ diffusion (in particular synaptic vesicles) influence recruitment or priming of vesicles for release. Vesicular recruitment is strongly influenced by the separation distance between an opened calcium channel and the target controlling release, and by the concentration and binding properties of the intracellular buffers, as in previous models. When a single opened calcium channel is very close to the target, a single synaptic vesicle can be recruited. However, many of the single-channel openings actuated by a nerve impulse are likely to be ineffective for release, although they contribute to the buildup of total intracellular Ca2+. Thus, the overall effectiveness of single calcium channels in causing vesicles to undergo exocytosis is likely quite low.Key words: synapse, Monte Carlo simulation, synaptic vesicle, active zone, vesicle recruitment, crayfish, calcium, calcium buffer.

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