scholarly journals Synapsins and the Synaptic Vesicle Reserve Pool: Floats or Anchors?

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 658
Author(s):  
Minchuan Zhang ◽  
George J. Augustine
Keyword(s):  
Liquid Phase ◽  
Experimental Evidence ◽  
Synaptic Vesicle ◽  
Synaptic Vesicles ◽  
Synaptic Activity ◽  
Cross Linking ◽  
Presynaptic Terminals ◽  
Reserve Pool

In presynaptic terminals, synaptic vesicles (SVs) are found in a discrete cluster that includes a reserve pool that is mobilized during synaptic activity. Synapsins serve as a key protein for maintaining SVs within this reserve pool, but the mechanism that allows synapsins to do this is unclear. This mechanism is likely to involve synapsins either cross-linking SVs, thereby anchoring SVs to each other, or creating a liquid phase that allows SVs to float within a synapsin droplet. Here, we summarize what is known about the role of synapsins in clustering of SVs and evaluate experimental evidence supporting these two models.

scholarly journals Colocalization of synapsin and actin during synaptic vesicle recycling

2003 ◽  
Vol 161 (4) ◽  
pp. 737-747 ◽  
Author(s):  
Ona Bloom ◽  
Emma Evergren ◽  
Nikolay Tomilin ◽  
Ole Kjaerulff ◽  
Peter Löw ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Synaptic Vesicle ◽  
Active Zone ◽  
Synaptic Vesicles ◽  
Synaptic Activity ◽  
Immunogold Electron Microscopy ◽  
Synaptic Vesicle Recycling ◽  
Vesicle Recycling ◽  
Reserve Pool ◽  
Giant Synapse

It has been hypothesized that in the mature nerve terminal, interactions between synapsin and actin regulate the clustering of synaptic vesicles and the availability of vesicles for release during synaptic activity. Here, we have used immunogold electron microscopy to examine the subcellular localization of actin and synapsin in the giant synapse in lamprey at different states of synaptic activity. In agreement with earlier observations, in synapses at rest, synapsin immunoreactivity was preferentially localized to a portion of the vesicle cluster distal to the active zone. During synaptic activity, however, synapsin was detected in the pool of vesicles proximal to the active zone. In addition, actin and synapsin were found colocalized in a dynamic filamentous cytomatrix at the sites of synaptic vesicle recycling, endocytic zones. Synapsin immunolabeling was not associated with clathrin-coated intermediates but was found on vesicles that appeared to be recycling back to the cluster. Disruption of synapsin function by microinjection of antisynapsin antibodies resulted in a prominent reduction of the cytomatrix at endocytic zones of active synapses. Our data suggest that in addition to its known function in clustering of vesicles in the reserve pool, synapsin migrates from the synaptic vesicle cluster and participates in the organization of the actin-rich cytomatrix in the endocytic zone during synaptic activity.

P.0557 A role of endophilin A in the synaptic vesicle liquid phase

2021 ◽  
Vol 53 ◽  
pp. S409-S410
Author(s):  
E. Sopova ◽  
O. Korenkova ◽  
K. Onochin ◽  
L. Brodin ◽  
O. Shupliakov
Keyword(s):  
Liquid Phase ◽  
Synaptic Vesicle

scholarly journals The dual role of chloride in synaptic vesicle glutamate transport

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Roger Chang ◽  
Jacob Eriksen ◽  
Robert H Edwards
Keyword(s):  
Synaptic Vesicle ◽  
Indirect Effects ◽  
Synaptic Vesicles ◽  
Transmembrane Domain ◽  
Dose Dependence ◽  
Direct Effects ◽  
Allosteric Activation ◽  
Vesicular Glutamate Transporters ◽  
Cl Conductance

The transport of glutamate into synaptic vesicles exhibits an unusual form of regulation by Cl- as well as an associated Cl- conductance. To distinguish direct effects of Cl- on the transporter from indirect effects via the driving force Δψ, we used whole endosome recording and report the first currents due to glutamate flux by the vesicular glutamate transporters (VGLUTs). Chloride allosterically activates the VGLUTs from both sides of the membrane, and we find that neutralization of an arginine in transmembrane domain four suffices for the lumenal activation. The dose dependence suggests that Cl- permeates through a channel and glutamate through a transporter. Competition between the anions nonetheless indicates that they use a similar permeation pathway. By controlling both ionic gradients and Δψ, endosome recording isolates different steps in the process of synaptic vesicle filling, suggesting distinct roles for Cl- in both allosteric activation and permeation.

scholarly journals Synuclein Regulates Synaptic Vesicle Clustering and Docking at a Vertebrate Synapse

2021 ◽  
Vol 9 ◽  
Author(s):  
Kaitlyn E. Fouke ◽  
M. Elizabeth Wegman ◽  
Sarah A. Weber ◽  
Emily B. Brady ◽  
Cristina Román-Vendrell ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Active Zone ◽  
Synaptic Vesicles ◽  
Significant Loss ◽  
Binding Partner ◽  
Reserve Pool ◽  
Associated Proteins ◽  
Dose Dependent ◽  
Total Membrane ◽  
Synapsin 1

Neurotransmission relies critically on the exocytotic release of neurotransmitters from small synaptic vesicles (SVs) at the active zone. Therefore, it is essential for neurons to maintain an adequate pool of SVs clustered at synapses in order to sustain efficient neurotransmission. It is well established that the phosphoprotein synapsin 1 regulates SV clustering at synapses. Here, we demonstrate that synuclein, another SV-associated protein and synapsin binding partner, also modulates SV clustering at a vertebrate synapse. When acutely introduced to unstimulated lamprey reticulospinal synapses, a pan-synuclein antibody raised against the N-terminal domain of α-synuclein induced a significant loss of SVs at the synapse. Both docked SVs and the distal reserve pool of SVs were depleted, resulting in a loss of total membrane at synapses. In contrast, antibodies against two other abundant SV-associated proteins, synaptic vesicle glycoprotein 2 (SV2) and vesicle-associated membrane protein (VAMP/synaptobrevin), had no effect on the size or distribution of SV clusters. Synuclein perturbation caused a dose-dependent reduction in the number of SVs at synapses. Interestingly, the large SV clusters appeared to disperse into smaller SV clusters, as well as individual SVs. Thus, synuclein regulates clustering of SVs at resting synapses, as well as docking of SVs at the active zone. These findings reveal new roles for synuclein at the synapse and provide critical insights into diseases associated with α-synuclein dysfunction, such as Parkinson’s disease.

scholarly journals A dynamin 1-, dynamin 3- and clathrin-independent pathway of synaptic vesicle recycling mediated by bulk endocytosis

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Yumei Wu ◽  
Eileen T O'Toole ◽  
Martine Girard ◽  
Brigitte Ritter ◽  
Mirko Messa ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Synaptic Vesicles ◽  
Synaptic Activity ◽  
Synaptic Vesicle Recycling ◽  
Knock Out ◽  
Knock Down ◽  
Vesicle Recycling ◽  
Subsequent Conversion ◽  
Insight Into

The exocytosis of synaptic vesicles (SVs) elicited by potent stimulation is rapidly compensated by bulk endocytosis of SV membranes leading to large endocytic vacuoles (‘bulk’ endosomes). Subsequently, these vacuoles disappear in parallel with the reappearance of new SVs. We have used synapses of dynamin 1 and 3 double knock-out neurons, where clathrin-mediated endocytosis (CME) is dramatically impaired, to gain insight into the poorly understood mechanisms underlying this process. Massive formation of bulk endosomes was not defective, but rather enhanced, in the absence of dynamin 1 and 3. The subsequent conversion of bulk endosomes into SVs was not accompanied by the accumulation of clathrin coated buds on their surface and this process proceeded even after further clathrin knock-down, suggesting its independence of clathrin. These findings support the existence of a pathway for SV reformation that bypasses the requirement for clathrin and dynamin 1/3 and that operates during intense synaptic activity.

scholarly journals Quantitative analysis of the native presynaptic cytomatrix by cryoelectron tomography

2010 ◽  
Vol 188 (1) ◽  
pp. 145-156 ◽  
Author(s):  
Rubén Fernández-Busnadiego ◽  
Benoît Zuber ◽  
Ulrike Elisabeth Maurer ◽  
Marek Cyrklaff ◽  
Wolfgang Baumeister ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Attachment Protein ◽  
Readily Releasable Pool ◽  
Protein Receptor ◽  
Membrane Contact ◽  
Synaptic Vesicle Release ◽  
Protein Attachment

The presynaptic terminal contains a complex network of filaments whose precise organization and functions are not yet understood. The cryoelectron tomography experiments reported in this study indicate that these structures play a prominent role in synaptic vesicle release. Docked synaptic vesicles did not make membrane to membrane contact with the active zone but were instead linked to it by tethers of different length. Our observations are consistent with an exocytosis model in which vesicles are first anchored by long (>5 nm) tethers that give way to multiple short tethers once vesicles enter the readily releasable pool. The formation of short tethers was inhibited by tetanus toxin, indicating that it depends on soluble N-ethyl-maleimide sensitive fusion protein attachment protein receptor complex assembly. Vesicles were extensively interlinked via a set of connectors that underwent profound rearrangements upon synaptic stimulation and okadaic acid treatment, suggesting a role of these connectors in synaptic vesicle mobilization and neurotransmitter release.

scholarly journals Cross-linking mass spectrometry uncovers protein interactions and functional assemblies in synaptic vesicle membranes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sabine Wittig ◽  
Marcelo Ganzella ◽  
Marie Barth ◽  
Susann Kostmann ◽  
Dietmar Riedel ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Synaptic Vesicle ◽  
Protein Interactions ◽  
Synaptic Vesicles ◽  
Large Scale ◽  
Cross Linking ◽  
Synaptic Membrane ◽  
Biophysical Parameters ◽  
Vesicle Membrane ◽  
Pass Through

AbstractSynaptic vesicles are storage organelles for neurotransmitters. They pass through a trafficking cycle and fuse with the pre-synaptic membrane when an action potential arrives at the nerve terminal. While molecular components and biophysical parameters of synaptic vesicles have been determined, our knowledge on the protein interactions in their membranes is limited. Here, we apply cross-linking mass spectrometry to study interactions of synaptic vesicle proteins in an unbiased approach without the need for specific antibodies or detergent-solubilisation. Our large-scale analysis delivers a protein network of vesicle sub-populations and functional assemblies including an active and an inactive conformation of the vesicular ATPase complex as well as non-conventional arrangements of the luminal loops of SV2A, Synaptophysin and structurally related proteins. Based on this network, we specifically target Synaptobrevin-2, which connects with many proteins, in different approaches. Our results allow distinction of interactions caused by ‘crowding’ in the vesicle membrane from stable interaction modules.

scholarly journals Protein–protein interactions and protein modules in the control of neurotransmitter release

1999 ◽  
Vol 354 (1381) ◽  
pp. 243-257 ◽  
Author(s):  
Fabio Benfenati ◽  
Franco Onofri ◽  
Silvia Giovedí
Keyword(s):  
Synaptic Vesicle ◽  
Protein Interactions ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Physiological Role ◽  
Presynaptic Membrane ◽  
Protein Protein Interactions ◽  
Sequence Of Events ◽  
Reserve Pool ◽  
Protein Modules

Information transfer among neurons is operated by neurotransmitters stored in synaptic vesicles and released to the extracellular space by an efficient process of regulated exocytosis. Synaptic vesicles are organized into two distinct functional pools, a large reserve pool in which vesicles are restrained by the actin–based cytoskeleton, and a quantitatively smaller releasable pool in which vesicles approach the presynaptic membrane and eventually fuse with it on stimulation. Both synaptic vesicle trafficking and neurotransmitter release depend on a precise sequence of events that include release from the reserve pool, targeting to the active zone, docking, priming, fusion and endocytotic retrieval of synaptic vesicles. These steps are mediated by a series of specific interactions among cytoskeletal, synaptic vesicle, presynaptic membrane and cytosolic proteins that, by acting in concert, promote the spatial and temporal regulation of the exocytotic machinery. The majority of these interactions are mediated by specific protein modules and domains that are found in many proteins and are involved in numerous intracellular processes. In this paper, the possible physiological role of these multiple protein–protein interactions is analysed, with ensuing updating and clarification of the present molecular model of the process of neurotransmitter release.

Sign in / Sign up

Export Citation Format

Share Document