scholarly journals Resolving the molecular architecture of the photoreceptor active zone by MINFLUX nanoscopy

2021 ◽  
Author(s):  
Chad Grabner ◽  
Isabella Jansen ◽  
Jakob Neef ◽  
Tobias Weiss ◽  
Roman Schmidt ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Molecular Complex ◽  
Active Zone ◽  
Single Layer ◽  
Release Site ◽  
Molecular Architecture ◽  
Synaptic Ribbon ◽  
Rod Photoreceptors ◽  
Macromolecular Complexes ◽  
Axis Of Symmetry

Cells assemble macromolecular complexes into scaffoldings that serve as substrates for catalytic processes. Years of molecular neurobiology indicate that neurotransmission depends on such optimization strategies, yet the molecular topography of the presynaptic Active Zone (AZ) where transmitter is released upon synaptic vesicle (SV) fusion remains to be visualized. Therefore, we implemented MINFLUX optical nanoscopy to resolve the AZ of rod photoreceptors. To facilitate MINFLUX nanoscopy of the AZ, we developed and verified an immobilization technique, we name Heat Assisted Rapid Dehydration (HARD). Here fresh retinal slices are directly stamped onto glass coverslips yielding a single layer of rod AZs. These AZs exhibited excellent labeling efficiency and minimal signal redundancy in the Z-direction. Our data indicate that the SV release site is a molecular complex of bassoon-Rab3-binding molecule 2 (RIM2)-ubMunc13-2-CAST. The complexes are serially duplicated longitudinally, and reflected in register along the axis of symmetry of the synaptic ribbon.

scholarly journals (M)Unc13s in Active Zone Diversity: A Drosophila Perspective

2022 ◽  
Vol 13 ◽  
Author(s):  
Chengji Piao ◽  
Stephan J. Sigrist
Keyword(s):  
Synaptic Vesicle ◽  
Active Zone ◽  
Stoichiometric Composition ◽  
Release Site ◽  
Homeostatic Plasticity ◽  
Release Factor ◽  
Loosely Coupled ◽  
Action Potential Frequency ◽  
Active Zones ◽  
Potential Frequency

The so-called active zones at pre-synaptic terminals are the ultimate filtering devices, which couple between action potential frequency and shape, and the information transferred to the post-synaptic neurons, finally tuning behaviors. Within active zones, the release of the synaptic vesicle operates from specialized “release sites.” The (M)Unc13 class of proteins is meant to define release sites topologically and biochemically, and diversity between Unc13-type release factor isoforms is suspected to steer diversity at active zones. The two major Unc13-type isoforms, namely, Unc13A and Unc13B, have recently been described from the molecular to the behavioral level, exploiting Drosophila being uniquely suited to causally link between these levels. The exact nanoscale distribution of voltage-gated Ca2+ channels relative to release sites (“coupling”) at pre-synaptic active zones fundamentally steers the release of the synaptic vesicle. Unc13A and B were found to be either tightly or loosely coupled across Drosophila synapses. In this review, we reported recent findings on diverse aspects of Drosophila Unc13A and B, importantly, their nano-topological distribution at active zones and their roles in release site generation, active zone assembly, and pre-synaptic homeostatic plasticity. We compared their stoichiometric composition at different synapse types, reviewing the correlation between nanoscale distribution of these two isoforms and release physiology and, finally, discuss how isoform-specific release components might drive the functional heterogeneity of synapses and encode discrete behavior.

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 Coordinated bi-directional trafficking of synaptic vesicle and active zone proteins in peripheral nerves

2021 ◽  
Vol 559 ◽  
pp. 92-98
Author(s):  
Judyta K. Juranek ◽  
Konark Mukherjee ◽  
Reinhard Jahn ◽  
Jia-Yi Li
Keyword(s):  
Synaptic Vesicle ◽  
Peripheral Nerves ◽  
Active Zone

scholarly journals The DISABLED protein functions in CLATHRIN-mediated synaptic vesicle endocytosis and exoendocytic coupling at the active zone

2011 ◽  
Vol 108 (25) ◽  
pp. E222-E229 ◽  
Author(s):  
F. Kawasaki ◽  
J. Iyer ◽  
L. L. Posey ◽  
C. E. Sun ◽  
S. E. Mammen ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Active Zone ◽  
The Disabled ◽  
Protein Functions

scholarly journals Nanoscale dynamics of synaptic vesicle trafficking and fusion at the presynaptic active zone

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Thirumalini Vaithianathan ◽  
Diane Henry ◽  
Wendy Akmentin ◽  
Gary Matthews
Keyword(s):  
Active Zone ◽  
Synaptic Vesicles ◽  
Super Resolution ◽  
Visual Signals ◽  
Dual Function ◽  
Macromolecular Complex ◽  
Synaptic Ribbon ◽  
Modes Of Transmission ◽  
Resolution Imaging ◽  
Specialized Structure

The cytomatrix at the active zone (CAZ) is a macromolecular complex that facilitates the supply of release-ready synaptic vesicles to support neurotransmitter release at synapses. To reveal the dynamics of this supply process in living synapses, we used super-resolution imaging to track single vesicles at voltage-clamped presynaptic terminals of retinal bipolar neurons, whose CAZ contains a specialized structure—the synaptic ribbon—that supports both fast, transient and slow, sustained modes of transmission. We find that the synaptic ribbon serves a dual function as a conduit for diffusion of synaptic vesicles and a platform for vesicles to fuse distal to the plasma membrane itself, via compound fusion. The combination of these functions allows the ribbon-type CAZ to achieve the continuous transmitter release required by synapses of neurons that carry tonic, graded visual signals in the retina.

scholarly journals Synaptic vesicle dynamics in mouse rod bipolar cells

2008 ◽  
Vol 25 (4) ◽  
pp. 523-533 ◽  
Author(s):  
QUN-FANG WAN ◽  
ALEJANDRO VILA ◽  
ZHEN-YU ZHOU ◽  
RUTH HEIDELBERGER
Keyword(s):  
Synaptic Vesicle ◽  
Time Constant ◽  
Active Zone ◽  
Bipolar Cell ◽  
Visual Information ◽  
Membrane Surface ◽  
Bipolar Cells ◽  
Calcium Dependent ◽  
Vesicle Dynamics ◽  
Rod Bipolar Cells

AbstractTo better understand synaptic signaling at the mammalian rod bipolar cell terminal and pave the way for applying genetic approaches to the study of visual information processing in the mammalian retina, synaptic vesicle dynamics and intraterminal calcium were monitored in terminals of acutely isolated mouse rod bipolar cells and the number of ribbon-style active zones quantified. We identified a releasable pool, corresponding to a maximum of ≈35 vesicles/ribbon-style active zone. Following depletion, this pool was refilled with a time constant of ≈7 s. The presence of a smaller, rapidly releasing pool and a small, fast component of refilling was also suggested. Following calcium channel closure, membrane surface area was restored to baseline with a time constant that ranged from 2 to 21 s depending on the magnitude of the preceding Ca2+ transient. In addition, a brief, calcium-dependent delay often preceded the start of onset of membrane recovery. Thus, several aspects of synaptic vesicle dynamics appear to be conserved between rod-dominant bipolar cells of fish and mammalian rod bipolar cells. A major difference is that the number of vesicles available for release is significantly smaller in the mouse rod bipolar cell, both as a function of the total number per neuron and on a per active zone basis.

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.

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