2016
DOI: 10.7554/elife.15133
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Physical determinants of vesicle mobility and supply at a central synapse

Abstract: Encoding continuous sensory variables requires sustained synaptic signalling. At several sensory synapses, rapid vesicle supply is achieved via highly mobile vesicles and specialized ribbon structures, but how this is achieved at central synapses without ribbons is unclear. Here we examine vesicle mobility at excitatory cerebellar mossy fibre synapses which sustain transmission over a broad frequency bandwidth. Fluorescent recovery after photobleaching in slices from VGLUT1Venus knock-in mice reveal 75% of VGL… Show more

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Cited by 52 publications
(70 citation statements)
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References 86 publications
(187 reference statements)
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“…From a purely mechanistic point of view, the curbing of presynaptic release by the AZ matrix could be viewed as an example of endogenous macromolecular congestion impacting on cellular function, with the clustering state of the AZ matrix restricting the ingress of presynaptic molecules into the AZ, thus limiting the composition of the functional AZ machinery. Similar principles have been proposed to modulate synaptic vesicles dynamics through congestion by the actin cytoskeleton (Morales et al., 2000) or collisions with organelles (Rothman et al., 2016). It is worth considering that, in a broader scope of cell biology, nanoscale structural plasticity of macromolecular assemblies may play a role in other functionally relevant contexts in the cell, e.g., in receptor signaling (James and Vale, 2012), endosome sorting (Wallrabe et al., 2007), and gene expression (Tan et al., 2013).…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…From a purely mechanistic point of view, the curbing of presynaptic release by the AZ matrix could be viewed as an example of endogenous macromolecular congestion impacting on cellular function, with the clustering state of the AZ matrix restricting the ingress of presynaptic molecules into the AZ, thus limiting the composition of the functional AZ machinery. Similar principles have been proposed to modulate synaptic vesicles dynamics through congestion by the actin cytoskeleton (Morales et al., 2000) or collisions with organelles (Rothman et al., 2016). It is worth considering that, in a broader scope of cell biology, nanoscale structural plasticity of macromolecular assemblies may play a role in other functionally relevant contexts in the cell, e.g., in receptor signaling (James and Vale, 2012), endosome sorting (Wallrabe et al., 2007), and gene expression (Tan et al., 2013).…”
Section: Discussionmentioning
confidence: 99%
“…This tight arrangement is thought to result in a locally crowded molecular environment (Morales et al., 2000, Rothman et al., 2016, Wilhelm et al., 2014), that could lead to competition for space between AZ proteins. Due to its high molecular weight (410 kDa) and large estimated numbers (>400 molecules per AZ) (Wilhelm et al., 2014), the matrix protein Bassoon (Bsn) is estimated to account for a large proportion of the AZ matrix material.…”
Section: Introductionmentioning
confidence: 99%
“…Thus, by changing the strength of phase separation of SVs in clusters, mammalian VGLUT1 may influence glutamate release parameters. It remains to establish how neurons use this feature of VGLUT1 to locally modulate quantal release by changing SV mobility stages at selected synapses (Herzog et al, 2011;Rothman et al, 2016;Staras et al, 2010). Table 1: List of mutant constructs tested.…”
Section: Mammalian Vglut1 Acts As a Dual Regulator Of Glutamate Releasementioning
confidence: 99%
“…It is conceivable that the MNTB–LSO synapses contain specialized and thus more efficient mechanisms for this vesicle mobilization process, perhaps via reduced viscosity in the cytoplasm (Rothman et al . ); however, the molecular machinery involved remains unknown. Similarly, synaptic vesicle membrane retrieval may occur via different endocytic pathways with distinct kinetics (Delvendahl et al .…”
mentioning
confidence: 99%
“…Although the mechanisms regulating synaptic vesicle exocytosis are fairly well understood (Südhof, 2004), mobilization of synaptic vesicles from a hypothesized reserve pool to the readily releasable pool during ongoing activity is less well understood. It is conceivable that the MNTB-LSO synapses contain specialized and thus more efficient mechanisms for this vesicle mobilization process, perhaps via reduced viscosity in the cytoplasm (Rothman et al 2016); however, the molecular machinery involved remains unknown. Similarly, synaptic vesicle membrane retrieval may occur via different endocytic pathways with distinct kinetics (Delvendahl et al 2016).…”
mentioning
confidence: 99%