Nano-Organization at the Synapse: Segregation of Distinct Forms of Neurotransmission

Frontiers in Synaptic Neuroscience ◽

10.3389/fnsyn.2021.796498 ◽

2021 ◽

Vol 13 ◽

Author(s):

Natalie J. Guzikowski ◽

Ege T. Kavalali

Keyword(s):

Active Zone ◽

Structural Organization ◽

Physiological Significance ◽

Synaptic Efficacy ◽

Biochemical Pathways ◽

Molecular Components ◽

Single Synapse

Synapses maintain synchronous, asynchronous, and spontaneous modes of neurotransmission through distinct molecular and biochemical pathways. Traditionally a single synapse was assumed to have a homogeneous organization of molecular components both at the active zone and post-synaptically. However, recent advancements in experimental tools and the further elucidation of the physiological significance of distinct forms of release have challenged this notion. In comparison to rapid evoked release, the physiological significance of both spontaneous and asynchronous neurotransmission has only recently been considered in parallel with synaptic structural organization. Active zone nanostructure aligns with postsynaptic nanostructure creating a precise trans-synaptic alignment of release sites and receptors shaping synaptic efficacy, determining neurotransmission reliability, and tuning plasticity. This review will discuss how studies delineating synaptic nanostructure create a picture of a molecularly heterogeneous active zone tuned to distinct forms of release that may dictate diverse synaptic functional outputs.

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Complexin cooperates with Bruchpilot to tether synaptic vesicles to the active zone cytomatrix

The Journal of Cell Biology ◽

10.1083/jcb.201806155 ◽

2019 ◽

Vol 218 (3) ◽

pp. 1011-1026 ◽

Cited By ~ 6

Author(s):

Nicole Scholz ◽

Nadine Ehmann ◽

Divya Sachidanandan ◽

Cordelia Imig ◽

Benjamin H. Cooper ◽

...

Keyword(s):

Protein Interactions ◽

Active Zone ◽

Synaptic Vesicles ◽

Snare Complex ◽

C Terminus ◽

Unknown Protein ◽

Transmission Part ◽

Molecular Components ◽

In Vivo Screen

Information processing by the nervous system depends on neurotransmitter release from synaptic vesicles (SVs) at the presynaptic active zone. Molecular components of the cytomatrix at the active zone (CAZ) regulate the final stages of the SV cycle preceding exocytosis and thereby shape the efficacy and plasticity of synaptic transmission. Part of this regulation is reflected by a physical association of SVs with filamentous CAZ structures via largely unknown protein interactions. The very C-terminal region of Bruchpilot (Brp), a key component of the Drosophila melanogaster CAZ, participates in SV tethering. Here, we identify the conserved SNARE regulator Complexin (Cpx) in an in vivo screen for molecules that link the Brp C terminus to SVs. Brp and Cpx interact genetically and functionally. Both proteins promote SV recruitment to the Drosophila CAZ and counteract short-term synaptic depression. Analyzing SV tethering to active zone ribbons of cpx3 knockout mice supports an evolutionarily conserved role of Cpx upstream of SNARE complex assembly.

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The presynaptic active zone: A dynamic scaffold that regulates synaptic efficacy

Experimental Cell Research ◽

10.1016/j.yexcr.2015.02.011 ◽

2015 ◽

Vol 335 (2) ◽

pp. 157-164 ◽

Cited By ~ 14

Author(s):

Katrin Michel ◽

Johannes Alexander Müller ◽

Ana-Maria Oprişoreanu ◽

Susanne Schoch

Keyword(s):

Active Zone ◽

Synaptic Efficacy ◽

Presynaptic Active Zone

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A comparison of active zone structure in frog neuromuscular junctions from two fast muscles with different synaptic efficacy

Journal of Neurocytology ◽

10.1007/bf01611734 ◽

1986 ◽

Vol 15 (4) ◽

pp. 525-534 ◽

Cited By ~ 22

Author(s):

Jon W. Propst ◽

Albert A. Herrera ◽

Chien -Ping Ko

Keyword(s):

Active Zone ◽

Neuromuscular Junctions ◽

Synaptic Efficacy ◽

Zone Structure ◽

Fast Muscles

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Complexin cooperates with Bruchpilot to tether synaptic vesicles to the active zone cytomatrix

10.1101/350207 ◽

2018 ◽

Author(s):

Nicole Scholz ◽

Nadine Ehmann ◽

Divya Sachidanandan ◽

Cordelia Imig ◽

Benjamin H. Cooper ◽

...

Keyword(s):

Protein Interactions ◽

Active Zone ◽

Synaptic Vesicles ◽

Bipolar Cells ◽

Snare Complex ◽

Protein Receptor ◽

C Terminus ◽

Transmission Part ◽

Molecular Components

ABSTRACTInformation processing by the nervous system depends on the release of neurotransmitter from synaptic vesicles (SVs) at the presynaptic active zone. Molecular components of the cytomatrix at the active zone (CAZ) regulate the final stages of the SV cycle preceding exocytosis and thereby shape the efficacy and plasticity of synaptic transmission. Part of this regulation is reflected by a physical association of SVs with filamentous CAZ structures. However, our understanding of the protein interactions underlying SV tethering by the CAZ is far from complete. The very C-terminal region of Bruchpilot (Brp), a key component of the Drosophila CAZ, participates in SV tethering. Yet so far, no vesicular or cytoplasmic molecules have been reported to engage in an interaction with Brp’s C-terminus. Here, we carried out an in vivo screen for molecules that link the Brp C-terminus to SVs. This strategy identified the conserved SNARE (soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor) regulator Complexin (Cpx) as a vesicular interaction partner of Brp. We show that Brp and Cpx interact genetically and functionally. Interfering with Cpx targeting to SVs mirrored distinctive features of a C-terminal Brp truncation: impaired SV recruitment to the CAZ and enhanced short-term synaptic depression. Extending the study beyond Drosophila synapses, we interrogated active zones of mouse rod bipolar cells. Here, too, we collected evidence for an evolutionarily conserved role of Cpx upstream of SNARE complex assembly where it participates in SV tethering to the CAZ.

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Structural organization of escherichia coli ribosomes as determined by immuno electron microscopy

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100081693 ◽

1978 ◽

Vol 36 (2) ◽

pp. 166-167 ◽

Cited By ~ 1

Author(s):

G. Stöffler ◽

R.W. Bald ◽

J. Dieckhoff ◽

H. Eckhard ◽

R. Lührmann ◽

...

Keyword(s):

Electron Microscopy ◽

Escherichia Coli ◽

Ribosomal Proteins ◽

Structural Organization ◽

Three Dimensional ◽

Ribosomal Subunit ◽

Spatial Arrangement ◽

Small Subunit ◽

Antibody Binding ◽

Immuno Electron Microscopy

A central step towards an understanding of the structure and function of the Escherichia coli ribosome, a large multicomponent assembly, is the elucidation of the spatial arrangement of its 54 proteins and its three rRNA molecules. The structural organization of ribosomal components has been investigated by a number of experimental approaches. Specific antibodies directed against each of the 54 ribosomal proteins of Escherichia coli have been performed to examine antibody-subunit complexes by electron microscopy. The position of the bound antibody, specific for a particular protein, can be determined; it indicates the location of the corresponding protein on the ribosomal surface.The three-dimensional distribution of each of the 21 small subunit proteins on the ribosomal surface has been determined by immuno electron microscopy: the 21 proteins have been found exposed with altogether 43 antibody binding sites. Each one of 12 proteins showed antibody binding at remote positions on the subunit surface, indicating highly extended conformations of the proteins concerned within the 30S ribosomal subunit; the remaining proteins are, however, not necessarily globular in shape (Fig. 1).

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Ribosome Structural Organization

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100051670 ◽

1974 ◽

Vol 32 ◽

pp. 332-333

Author(s):

James A. Lake

Keyword(s):

Ribosomal Proteins ◽

Structural Organization ◽

Three Dimensional ◽

Small Subunit ◽

Structural Studies ◽

X Ray Diffraction ◽

Specific Antibodies ◽

X Ray ◽

E Coli ◽

Complete Sequences

The understanding of ribosome structure has advanced considerably in the last several years. Biochemists have characterized the constituent proteins and rRNA's of ribosomes. Complete sequences have been determined for some ribosomal proteins and specific antibodies have been prepared against all E. coli small subunit proteins. In addition, a number of naturally occuring systems of three dimensional ribosome crystals which are suitable for structural studies have been observed in eukaryotes. Although the crystals are, in general, too small for X-ray diffraction, their size is ideal for electron microscopy.

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Study of the Molecular Architecture of Keratin Filaments by Electron Microscopy

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053310 ◽

1982 ◽

Vol 40 ◽

pp. 118-119

Author(s):

U. Aebi ◽

P. Rew ◽

T.-T. Sun

Keyword(s):

Electron Microscopy ◽

Structural Organization ◽

Cell Types ◽

Structural Features ◽

Molecular Architecture ◽

The Past ◽

Keratin Filaments ◽

Different Types ◽

10 Nm Filaments ◽

Different Cell Types

Various types of intermediate-sized (10-nm) filaments have been found and described in many different cell types during the past few years. Despite the differences in the chemical composition among the different types of filaments, they all yield common structural features: they are usually up to several microns long and have a diameter of 7 to 10 nm; there is evidence that they are made of several 2 to 3.5 nm wide protofilaments which are helically wound around each other; the secondary structure of the polypeptides constituting the filaments is rich in ∞-helix. However a detailed description of their structural organization is lacking to date.

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Microscopic investigations of novel intracellular bodies of a Nocardia SP

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100169511 ◽

1994 ◽

Vol 52 ◽

pp. 356-357

Author(s):

J. L. Stites

Keyword(s):

Uranyl Acetate ◽

Electron Microscopic ◽

En Bloc ◽

Ribonucleic Acids ◽

Transmission Electron ◽

Nocardia Sp ◽

Internal Constitution ◽

Membrane Bound ◽

Molecular Components ◽

Protein Rich

A Nocardia sp.was found during an initial transmission electron microscopic (TEM) examination to have unusual intracellular bodies (ICB's) which do not appear to have been described previously in the literature. Most intracellular structures within bacteria have been classified as storage granules, a product of membrane invagination (i.e. mesosomes), or vacuoles. In bacteria there are no known intracellular membrane-bound organelles, and all internal membranes are invaginations of the unit membrane. Several microscopic-level examinations of the Nocardia sp. ICB's were initiated in order to determine their overall structure, classification, and internal constitution.Different TEM staining procedures were performed to determine possible molecular components of the ICB. In all of the staining protocols the ICB's showed a lack of electron density similar to the cell wall. Because the ICB's showed no affinity to any stain, it appeared they do not have strong positive charge (phosphotungstic acid), are not protein rich (en bloc uranyl acetate), lack glycogen and are not phosphate or sulphur rich (lead citrate), nor do they contain lipids or ribonucleic acids (osmium tetroxide).

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