scholarly journals Physical and functional interaction of the active zone proteins, CAST, RIM1, and Bassoon, in neurotransmitter release

2004 ◽  
Vol 164 (2) ◽  
pp. 301-311 ◽  
Author(s):  
Etsuko Takao-Rikitsu ◽  
Sumiko Mochida ◽  
Eiji Inoue ◽  
Maki Deguchi-Tawarada ◽  
Marie Inoue ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Active Zone ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Ternary Complex ◽  
Binding Region ◽  
Functional Interaction ◽  
Cervical Ganglion ◽  
Ganglion Neurons ◽  
The Brain

We have recently isolated a novel cytomatrix at the active zone (CAZ)–associated protein, CAST, and found it directly binds another CAZ protein RIM1 and indirectly binds Munc13-1 through RIM1; RIM1 and Munc13-1 directly bind to each other and are implicated in priming of synaptic vesicles. Here, we show that all the CAZ proteins thus far known form a large molecular complex in the brain, including CAST, RIM1, Munc13-1, Bassoon, and Piccolo. RIM1 and Bassoon directly bind to the COOH terminus and central region of CAST, respectively, forming a ternary complex. Piccolo, which is structurally related to Bassoon, also binds to the Bassoon-binding region of CAST. Moreover, the microinjected RIM1- or Bassoon-binding region of CAST impairs synaptic transmission in cultured superior cervical ganglion neurons. Furthermore, the CAST-binding domain of RIM1 or Bassoon also impairs synaptic transmission in the cultured neurons. These results indicate that CAST serves as a key component of the CAZ structure and is involved in neurotransmitter release by binding these CAZ proteins.

Neurotransmitter Release

2017 ◽  
Author(s):  
Peggy Mason
Keyword(s):  
Plasma Membrane ◽  
Synaptic Vesicle ◽  
Active Zone ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Synaptic Cleft ◽  
Fusion Pore ◽  
Synaptic Membrane ◽  
Specialized Region ◽  
Synaptic Vesicle Fusion

The biochemical and physiological processes of neurotransmitter release from an active zone, a specialized region of synaptic membrane, are examined. Synaptic vesicles containing neurotransmitters are docked at the active zone and then primed for release by SNARE complexes that bring them into extreme proximity to the plasma membrane. Entry of calcium ions through voltage-gated calcium channels triggers synaptic vesicle fusion with the synaptic terminal membrane and the consequent diffusion of neurotransmitter into the synaptic cleft. Release results when the fusion pore bridging the synaptic vesicle and plasma membrane widens and neurotransmitter from the inside of the synaptic vesicle diffuses into the synaptic cleft. Membrane from the active zone membrane is endocytosed, and synaptic vesicle proteins are then reassembled into recycled synaptic vesicles, allowing for more rounds of neurotransmitter release.

scholarly journals Fife organizes synaptic vesicles and calcium channels for high-probability neurotransmitter release

2016 ◽  
Vol 216 (1) ◽  
pp. 231-246 ◽  
Author(s):  
Joseph J. Bruckner ◽  
Hong Zhan ◽  
Scott J. Gratz ◽  
Monica Rao ◽  
Fiona Ukken ◽  
...  
Keyword(s):  
Neural Plasticity ◽  
Active Zone ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Motor Behavior ◽  
Molecular Organization ◽  
Electrophysiological Studies ◽  
Circuit Function ◽  
Synaptic Vesicle Release ◽  
Ca2 Channels

The strength of synaptic connections varies significantly and is a key determinant of communication within neural circuits. Mechanistic insight into presynaptic factors that establish and modulate neurotransmitter release properties is crucial to understanding synapse strength, circuit function, and neural plasticity. We previously identified Drosophila Piccolo-RIM-related Fife, which regulates neurotransmission and motor behavior through an unknown mechanism. Here, we demonstrate that Fife localizes and interacts with RIM at the active zone cytomatrix to promote neurotransmitter release. Loss of Fife results in the severe disruption of active zone cytomatrix architecture and molecular organization. Through electron tomographic and electrophysiological studies, we find a decrease in the accumulation of release-ready synaptic vesicles and their release probability caused by impaired coupling to Ca2+ channels. Finally, we find that Fife is essential for the homeostatic modulation of neurotransmission. We propose that Fife organizes active zones to create synaptic vesicle release sites within nanometer distance of Ca2+ channel clusters for reliable and modifiable neurotransmitter release.

scholarly journals LGI1–ADAM22–MAGUK configures transsynaptic nanoalignment for synaptic transmission and epilepsy prevention

2021 ◽  
Vol 118 (3) ◽  
pp. e2022580118
Author(s):  
Yuko Fukata ◽  
Xiumin Chen ◽  
Satomi Chiken ◽  
Yoko Hirano ◽  
Atsushi Yamagata ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Ampa Receptors ◽  
Neurotransmitter Release ◽  
Epileptic Encephalopathy ◽  
Secreted Protein ◽  
Gene Products ◽  
Molecular Identity ◽  
Postsynaptic Receptors ◽  
Epilepsy Gene ◽  
The Brain

Physiological functioning and homeostasis of the brain rely on finely tuned synaptic transmission, which involves nanoscale alignment between presynaptic neurotransmitter-release machinery and postsynaptic receptors. However, the molecular identity and physiological significance of transsynaptic nanoalignment remain incompletely understood. Here, we report that epilepsy gene products, a secreted protein LGI1 and its receptor ADAM22, govern transsynaptic nanoalignment to prevent epilepsy. We found that LGI1–ADAM22 instructs PSD-95 family membrane-associated guanylate kinases (MAGUKs) to organize transsynaptic protein networks, including NMDA/AMPA receptors, Kv1 channels, and LRRTM4–Neurexin adhesion molecules. Adam22ΔC5/ΔC5 knock-in mice devoid of the ADAM22–MAGUK interaction display lethal epilepsy of hippocampal origin, representing the mouse model for ADAM22-related epileptic encephalopathy. This model shows less-condensed PSD-95 nanodomains, disordered transsynaptic nanoalignment, and decreased excitatory synaptic transmission in the hippocampus. Strikingly, without ADAM22 binding, PSD-95 cannot potentiate AMPA receptor-mediated synaptic transmission. Furthermore, forced coexpression of ADAM22 and PSD-95 reconstitutes nano-condensates in nonneuronal cells. Collectively, this study reveals LGI1–ADAM22–MAGUK as an essential component of transsynaptic nanoarchitecture for precise synaptic transmission and epilepsy prevention.

Postnatal rat sympathetic neurons in culture. II. Synaptic transmission by postnatal neurons

1979 ◽  
Vol 42 (5) ◽  
pp. 1426-1436 ◽  
Author(s):  
E. Wakshull ◽  
M. I. Johnson ◽  
H. Burton
Keyword(s):  
Skeletal Muscle ◽  
Synaptic Transmission ◽  
Sympathetic Neurons ◽  
Preceding Paper ◽  
Blocking Agent ◽  
Culture Conditions ◽  
Cervical Ganglion ◽  
Dissociated Cell Culture ◽  
Ganglion Neurons ◽  
Neurotransmitter Plasticity

1. It was shown in the preceding paper that postnatally derived rat superior cervical ganglion neurons (SCGN) will grow in dissociated cell culture and form functional synaptic connections with each other. In this report, synaptic transmission by the postnatal SCGN is detailed. 2. Synaptic interactions between SCGN were blocked by the nicotinic cholinergic antagonist hexamathonium (C-6), indicating that acetylcholine was the transmitter substance used by these neurons. This was found to be the case even for neurons taken from 12.5-wk-old animals. 3. In a few cases, the beta-adrenergic blocking agent, propranolol, was found to block synaptic potentials, suggesting that a catecholamine might be involved in the transmission process. The possible mechanisms of this involvement are discussed. 4. SCGN taken from up to 10-wk-old rats were able to form functional synaptic contacts with cocultured skeletal muscle cells. These interactions were sensitive to low external Ca2+ and to 1--2 microM d-tubocurarine (d-TC). 5. It is concluded that even adult SCGN retain a certain amount of neurotransmitter "plasticity" when grown under appropriate culture conditions. From the data on the neuron-neuron and SCGN-skeletal muscle interactions, it is suggested that a matching of presynaptic transmitter with postsynaptic receptor is a sufficient condition for the formation of functional nerve-target interactions.

scholarly journals RIM-BP2 primes synaptic vesicles via recruitment of Munc13-1 at hippocampal mossy fiber synapses

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Marisa M Brockmann ◽  
Marta Maglione ◽  
Claudia G Willmes ◽  
Alexander Stumpf ◽  
Boris A Bouazza ◽  
...  
Keyword(s):  
Active Zone ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Mossy Fiber ◽  
Substantial Impact ◽  
Vesicle Docking ◽  
Vesicular Release ◽  
Anatomical Properties ◽  
Presynaptic Protein ◽  
Determinant Factor

All synapses require fusion-competent vesicles and coordinated Ca2+-secretion coupling for neurotransmission, yet functional and anatomical properties are diverse across different synapse types. We show that the presynaptic protein RIM-BP2 has diversified functions in neurotransmitter release at different central murine synapses and thus contributes to synaptic diversity. At hippocampal pyramidal CA3-CA1 synapses, RIM-BP2 loss has a mild effect on neurotransmitter release, by only regulating Ca2+-secretion coupling. However, at hippocampal mossy fiber synapses, RIM-BP2 has a substantial impact on neurotransmitter release by promoting vesicle docking/priming and vesicular release probability via stabilization of Munc13-1 at the active zone. We suggest that differences in the active zone organization may dictate the role a protein plays in synaptic transmission and that differences in active zone architecture is a major determinant factor in the functional diversity of synapses.

scholarly journals Stable and Flexible Synaptic Transmission Controlled by the Active Zone Protein Interactions

2021 ◽  
Vol 22 (21) ◽  
pp. 11775
Author(s):  
Sumiko Mochida
Keyword(s):  
Synaptic Transmission ◽  
Protein Interactions ◽  
Active Zone ◽  
Synaptic Vesicles ◽  
Physiological Role ◽  
Release Site ◽  
Synaptic Vesicle Exocytosis ◽  
Vesicle Exocytosis ◽  
Presynaptic Plasma Membrane ◽  
Sensor Proteins

An action potential triggers neurotransmitter release from synaptic vesicles docking to a specialized release site of the presynaptic plasma membrane, the active zone. The active zone is a highly organized structure with proteins that serves as a platform for synaptic vesicle exocytosis, mediated by SNAREs complex and Ca2+ sensor proteins, within a sub-millisecond opening of nearby Ca2+ channels with the membrane depolarization. In response to incoming neuronal signals, each active zone protein plays a role in the release-ready site replenishment with synaptic vesicles for sustainable synaptic transmission. The active zone release apparatus provides a possible link between neuronal activity and plasticity. This review summarizes the mostly physiological role of active zone protein interactions that control synaptic strength, presynaptic short-term plasticity, and homeostatic synaptic plasticity.

scholarly journals Reduced endogenous Ca2+ buffering speeds active zone Ca2+ signaling

2015 ◽  
Vol 112 (23) ◽  
pp. E3075-E3084 ◽  
Author(s):  
Igor Delvendahl ◽  
Lukasz Jablonski ◽  
Carolin Baade ◽  
Victor Matveev ◽  
Erwin Neher ◽  
...  
Keyword(s):  
High Resolution ◽  
Synaptic Transmission ◽  
Active Zone ◽  
Neurotransmitter Release ◽  
Mossy Fiber ◽  
Repetitive Firing ◽  
Two Photon ◽  
High Affinity ◽  
Model Predictions ◽  
Active Zones

Fast synchronous neurotransmitter release at the presynaptic active zone is triggered by local Ca2+ signals, which are confined in their spatiotemporal extent by endogenous Ca2+ buffers. However, it remains elusive how rapid and reliable Ca2+ signaling can be sustained during repetitive release. Here, we established quantitative two-photon Ca2+ imaging in cerebellar mossy fiber boutons, which fire at exceptionally high rates. We show that endogenous fixed buffers have a surprisingly low Ca2+-binding ratio (∼15) and low affinity, whereas mobile buffers have high affinity. Experimentally constrained modeling revealed that the low endogenous buffering promotes fast clearance of Ca2+ from the active zone during repetitive firing. Measuring Ca2+ signals at different distances from active zones with ultra-high-resolution confirmed our model predictions. Our results lead to the concept that reduced Ca2+ buffering enables fast active zone Ca2+ signaling, suggesting that the strength of endogenous Ca2+ buffering limits the rate of synchronous synaptic transmission.

scholarly journals SAD: A Presynaptic Kinase Associated with Synaptic Vesicles and the Active Zone Cytomatrix that Regulates Neurotransmitter Release

Neuron ◽  
2006 ◽  
Vol 50 (2) ◽  
pp. 261-275 ◽  
Author(s):  
Eiji Inoue ◽  
Sumiko Mochida ◽  
Hiroshi Takagi ◽  
Susumu Higa ◽  
Maki Deguchi-Tawarada ◽  
...  
Keyword(s):  
Active Zone ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles

Regulation of cholinergic activity by the vesicular acetylcholine transporter

2013 ◽  
Vol 450 (2) ◽  
pp. 265-274 ◽  
Author(s):  
Vania F. Prado ◽  
Ashbeel Roy ◽  
Benjamin Kolisnyk ◽  
Robert Gros ◽  
Marco A. M. Prado
Keyword(s):  
Transmitter Release ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Cholinergic Neurons ◽  
Vesicular Acetylcholine Transporter ◽  
Cholinergic Activity ◽  
Neurotransmitter Transporter ◽  
Pathological Conditions ◽  
The Brain ◽  
Surprising Finding

Acetylcholine, the first chemical to be identified as a neurotransmitter, is packed in synaptic vesicles by the activity of VAChT (vesicular acetylcholine transporter). A decrease in VAChT expression has been reported in a number of diseases, and this has consequences for the amount of acetylcholine loaded in synaptic vesicles as well as for neurotransmitter release. Several genetically modified mice targeting the VAChT gene have been generated, providing novel models to understand how changes in VAChT affect transmitter release. A surprising finding is that most cholinergic neurons in the brain also can express a second type of vesicular neurotransmitter transporter that allows these neurons to secrete two distinct neurotransmitters. Thus a given neuron can use two neurotransmitters to regulate different physiological functions. In addition, recent data indicate that non-neuronal cells can also express the machinery used to synthesize and release acetylcholine. Some of these cells rely on VAChT to secrete acetylcholine with potential physiological consequences in the periphery. Hence novel functions for the oldest neurotransmitter known are emerging with the potential to provide new targets for the treatment of several pathological conditions.

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