Molecular Organization and Assembly of the Presynaptic Active Zone of Neurotransmitter Release

2006 ◽  
pp. 49-68 ◽  
Author(s):  
Anna Fejtova ◽  
Eckart D. Gundelfinger
Keyword(s):  
Active Zone ◽  
Neurotransmitter Release ◽  
Molecular Organization ◽  
Presynaptic Active Zone

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 S6 kinase localizes to the presynaptic active zone and functions with PDK1 to control synapse development

2011 ◽  
Vol 194 (6) ◽  
pp. 921-935 ◽  
Author(s):  
Ling Cheng ◽  
Cody Locke ◽  
Graeme W. Davis
Keyword(s):  
Active Zone ◽  
Neurotransmitter Release ◽  
Synaptic Function ◽  
Growth Factor Signaling ◽  
Neuron Type ◽  
S6 Kinase ◽  
Neuronal Dendrites ◽  
Presynaptic Boutons ◽  
Presynaptic Active Zone ◽  
Presynaptic Protein

The dimensions of neuronal dendrites, axons, and synaptic terminals are reproducibly specified for each neuron type, yet it remains unknown how these structures acquire their precise dimensions of length and diameter. Similarly, it remains unknown how active zone number and synaptic strength are specified relative the precise dimensions of presynaptic boutons. In this paper, we demonstrate that S6 kinase (S6K) localizes to the presynaptic active zone. Specifically, S6K colocalizes with the presynaptic protein Bruchpilot (Brp) and requires Brp for active zone localization. We then provide evidence that S6K functions downstream of presynaptic PDK1 to control synaptic bouton size, active zone number, and synaptic function without influencing presynaptic bouton number. We further demonstrate that PDK1 is also a presynaptic protein, though it is distributed more broadly. We present a model in which synaptic S6K responds to local extracellular nutrient and growth factor signaling at the synapse to modulate developmental size specification, including cell size, bouton size, active zone number, and neurotransmitter release.

Molecular organization of the presynaptic active zone

2006 ◽  
Vol 326 (2) ◽  
pp. 379-391 ◽  
Author(s):  
Susanne Schoch ◽  
Eckart D. Gundelfinger
Keyword(s):  
Active Zone ◽  
Molecular Organization ◽  
Presynaptic Active Zone

scholarly journals Neurexins regulate presynaptic GABAB-receptors at central synapses

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Fujun Luo ◽  
Alessandra Sclip ◽  
Sean Merrill ◽  
Thomas C. Südhof
Keyword(s):  
Active Zone ◽  
Neurotransmitter Release ◽  
Molecular Mechanisms ◽  
Pyramidal Neurons ◽  
Receptor Activation ◽  
Gabab Receptors ◽  
Inhibitory Synapses ◽  
Receptor Signaling ◽  
Ca1 Region ◽  
Presynaptic Active Zone

AbstractDiverse signaling complexes are precisely assembled at the presynaptic active zone for dynamic modulation of synaptic transmission and synaptic plasticity. Presynaptic GABAB-receptors nucleate critical signaling complexes regulating neurotransmitter release at most synapses. However, the molecular mechanisms underlying assembly of GABAB-receptor signaling complexes remain unclear. Here we show that neurexins are required for the localization and function of presynaptic GABAB-receptor signaling complexes. At four model synapses, excitatory calyx of Held synapses in the brainstem, excitatory and inhibitory synapses on hippocampal CA1-region pyramidal neurons, and inhibitory basket cell synapses in the cerebellum, deletion of neurexins rendered neurotransmitter release significantly less sensitive to GABAB-receptor activation. Moreover, deletion of neurexins caused a loss of GABAB-receptors from the presynaptic active zone of the calyx synapse. These findings extend the role of neurexins at the presynaptic active zone to enabling GABAB-receptor signaling, supporting the notion that neurexins function as central organizers of active zone signaling complexes.

Amyloid Precursor Protein Knockout Diminishes Synaptic Vesicle Proteins at the Presynaptic Active Zone in Mouse Brain

2014 ◽  
Vol 11 (10) ◽  
pp. 971-980 ◽  
Author(s):  
Melanie Laßek ◽  
Jens Weingarten ◽  
Amparo Acker-Palmer ◽  
Sandra Bajjalieh ◽  
Ulrike Muller ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Synaptic Vesicle ◽  
Mouse Brain ◽  
Active Zone ◽  
Precursor Protein ◽  
Presynaptic Active Zone ◽  
Vesicle Proteins

scholarly journals PKC-phosphorylation of Liprin-α3 triggers phase separation and controls presynaptic active zone structure

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Javier Emperador-Melero ◽  
Man Yan Wong ◽  
Shan Shan H. Wang ◽  
Giovanni de Nola ◽  
Hajnalka Nyitrai ◽  
...  
Keyword(s):  
Phase Separation ◽  
Active Zone ◽  
Neurotransmitter Release ◽  
Hippocampal Neurons ◽  
Phosphorylation Site ◽  
Double Knockout ◽  
Zone Structure ◽  
Presynaptic Nerve Terminal ◽  
Condensate Formation ◽  
And Function

AbstractThe active zone of a presynaptic nerve terminal defines sites for neurotransmitter release. Its protein machinery may be organized through liquid–liquid phase separation, a mechanism for the formation of membrane-less subcellular compartments. Here, we show that the active zone protein Liprin-α3 rapidly and reversibly undergoes phase separation in transfected HEK293T cells. Condensate formation is triggered by Liprin-α3 PKC-phosphorylation at serine-760, and RIM and Munc13 are co-recruited into membrane-attached condensates. Phospho-specific antibodies establish phosphorylation of Liprin-α3 serine-760 in transfected cells and mouse brain tissue. In primary hippocampal neurons of newly generated Liprin-α2/α3 double knockout mice, synaptic levels of RIM and Munc13 are reduced and the pool of releasable vesicles is decreased. Re-expression of Liprin-α3 restored these presynaptic defects, while mutating the Liprin-α3 phosphorylation site to abolish phase condensation prevented this rescue. Finally, PKC activation in these neurons acutely increased RIM, Munc13 and neurotransmitter release, which depended on the presence of phosphorylatable Liprin-α3. Our findings indicate that PKC-mediated phosphorylation of Liprin-α3 triggers its phase separation and modulates active zone structure and function.

scholarly journals Synaptophysin 1 Clears Synaptobrevin 2 from the Presynaptic Active Zone to Prevent Short-Term Depression

Cell Reports ◽  
2016 ◽  
Vol 14 (6) ◽  
pp. 1369-1381 ◽  
Author(s):  
Rajit Rajappa ◽  
Anne Gauthier-Kemper ◽  
Daniel Böning ◽  
Jana Hüve ◽  
Jürgen Klingauf
Keyword(s):  
Active Zone ◽  
Short Term ◽  
Presynaptic Active Zone

scholarly journals Phosphorylation triggers presynaptic phase separation of Liprin-α3 to control active zone structure

2020 ◽  
Author(s):  
Javier Emperador-Melero ◽  
Man Yan Wong ◽  
Shan Shan H. Wang ◽  
Giovanni de Nola ◽  
Tom Kirchhausen ◽  
...  
Keyword(s):  
Phase Separation ◽  
Active Zone ◽  
Neurotransmitter Release ◽  
Phosphorylation Site ◽  
Double Knockout ◽  
Zone Structure ◽  
And Function ◽  
Pkc Activation ◽  
Liquid Liquid Phase Separation

AbstractLiquid-liquid phase separation enables the assembly of membrane-less subcellular compartments, but testing its biological functions has been difficult. The presynaptic active zone, protein machinery in nerve terminals that defines sites for neurotransmitter release, may be organized through phase separation. Here, we discover that the active zone protein Liprin-α3 rapidly and reversibly undergoes phase separation upon phosphorylation by PKC at a single site. RIM and Munc13 are co-recruited to membrane-attached condensates, and phospho-specific antibodies establish Liprin-α3 phosphorylation in vivo. At synapses of newly generated Liprin-α2/α3 double knockout mice, RIM, Munc13 and the pool of releasable vesicles were reduced. Re-expression of Liprin-α3 restored these defects, but mutating the Liprin-α3 phosphorylation site to abolish phase condensation prevented rescue. Finally, PKC activation acutely increased RIM, Munc13 and neurotransmitter release, which depended on the presence of phosphorylatable Liprin-α3. We conclude that Liprin-α3 phosphorylation rapidly triggers presynaptic phase separation to modulate active zone structure and function.

scholarly journals Assembling the Presynaptic Active Zone

Neuron ◽  
2001 ◽  
Vol 29 (1) ◽  
pp. 131-143 ◽  
Author(s):  
Rong Grace Zhai ◽  
Hagit Vardinon-Friedman ◽  
Claudia Cases-Langhoff ◽  
Birgit Becker ◽  
Eckart D. Gundelfinger ◽  
...  
Keyword(s):  
Active Zone ◽  
Presynaptic Active Zone

scholarly journals Assembly of the presynaptic active zone

2020 ◽  
Vol 63 ◽  
pp. 95-103 ◽  
Author(s):  
Javier Emperador-Melero ◽  
Pascal S Kaeser
Keyword(s):  
Active Zone ◽  
Presynaptic Active Zone
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