Vesicle Clustering in a Living Synapse Depends on a Synapsin Region that Mediates Phase Separation

Pechstein, Arndt; Tomilin, N.V.; Fredrich, Kristin; Vorontsova, Olga; Sopova, Elena; Evergren, Emma; Haucke, Volker; Brodin, Lennart; Shupliakov, Oleg

doi:10.1016/j.celrep.2020.01.092

Cited by 83 publications

(71 citation statements)

References 48 publications

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“…An educated guess would be that synapsin phosphorylation is mediating such dispersion, favoring the increase in the RRP size. In fact, vesicle clustering at the presynaptic terminal is known to be mediated by the synapsin family of proteins [51,52] and synapsins contain a conserved PKA phosphorylation site (Serine9) [53] that, when phosphorylated, mediates synapsin dissociation from vesicles [54]. PKA-and synapsin-mediated modulation of vesicle availability has also been observed in cultured human neurons [43].…”

Section: Discussionmentioning

confidence: 99%

Recruitment of release sites underlies chemical presynaptic potentiation at hippocampal mossy fiber boutons

et al. 2021

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Synaptic plasticity is a cellular model for learning and memory. However, the expression mechanisms underlying presynaptic forms of plasticity are not well understood. Here, we investigate functional and structural correlates of presynaptic potentiation at large hippocampal mossy fiber boutons induced by the adenylyl cyclase activator forskolin. We performed 2-photon imaging of the genetically encoded glutamate sensor iGluu that revealed an increase in the surface area used for glutamate release at potentiated terminals. Time-gated stimulated emission depletion microscopy revealed no change in the coupling distance between P/Q-type calcium channels and release sites mapped by Munc13-1 cluster position. Finally, by high-pressure freezing and transmission electron microscopy analysis, we found a fast remodeling of synaptic ultrastructure at potentiated boutons: Synaptic vesicles dispersed in the terminal and accumulated at the active zones, while active zone density and synaptic complexity increased. We suggest that these rapid and early structural rearrangements might enable long-term increase in synaptic strength.

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Section: Discussionmentioning

confidence: 99%

Recruitment of release sites underlies chemical presynaptic potentiation at hippocampal mossy fiber boutons

et al. 2021

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“…The explanation can be found in the completely different molecular composition of endolysosomes and synaptic vesicles. Endolysosomes lack synapsins, which are key to restrict the mobility of synaptic vesicles and promote their clustering ( Orenbuch et al, 2012 ; Pechstein et al, 2020 ). Actually, glutamatergic synaptic vesicles present in retinal bipolar cell terminals, a type of ribbon synapse that lacks synapsin isoforms ( Mandell et al, 1990 ), display a diffusion coefficient of 0.015 μm 2 ·s −1 ( Holt et al, 2004 ).…”

Section: Discussionmentioning

confidence: 99%

Axon terminals control endolysosome diffusion to support synaptic remodelling

Terni

Llobet

2021

Life Sci. Alliance

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Endolysosomes are acidic organelles formed by the fusion of endosomes with lysosomes. In the presynaptic compartment they contribute to protein homeostasis, the maintenance of vesicle pools and synaptic stability. Here, we evaluated the mobility of endolysosomes found in axon terminals of olfactory sensory neurons of Xenopus tropicalis tadpoles. F-actin restricts the motion of these presynaptic acidic organelles which is characterized by a diffusion coefficient of 6.7 × 10−3 μm2·s−1. Local injection of secreted protein acidic and rich in cysteine (SPARC) in the glomerular layer of the olfactory bulb disrupts the structure of synaptic F-actin patches and increases the presence and mobility of endolysosomal organelles found in axon terminals. The increased motion of endolysosomes is localized to the presynaptic compartment and does not promote their access to axonal regions for retrograde transportation to the cell body. Local activation of synaptic degradation mechanisms mediated by SPARC coincides with a loss of the ability of tadpoles to detect waterborne odorants. Together, these observations show that the diffusion of presynaptic endolysosomes increases during conditions of synaptic remodelling to support their local degradative activity.

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“…An educated guess would be that synapsin phosphorylation is mediating such dispersion favoring the increase in the RRP size. In fact, vesicle clustering at the presynaptic terminal is known to be mediated by the synapsin family of proteins (Milovanovic et al, 2018;Pechstein et al, 2020) and synapsins contain a conserved PKA phosphorylation site (Serine9) (Czernik et al, 1987). PKA and synapsin mediated modulation of vesicle availability has been observed also in cultured human neurons (Patzke et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Increased and synchronous recruitment of release sites underlies hippocampal mossy fiber presynaptic potentiation

Orlando

Dvorzhak

Bruentgens

et al. 2020

Preprint

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Synaptic plasticity is a cellular model for learning and memory. However, the expression mechanisms underlying presynaptic forms of plasticity are not well understood. Here, we investigate functional and structural correlates of long-term potentiation at large hippocampal mossy fiber boutons induced by the adenylyl cyclase activator forskolin. We performed two-photon imaging of the genetically encoded glutamate sensor iGlu u that revealed an increase in the surface area used for glutamate release at potentiated terminals. Moreover, time-gated stimulated emission depletion microscopy revealed no change in the coupling distance between immunofluorescence signals from calcium channels and release sites. Finally, by high-pressure freezing and transmission electron microscopy analysis, we found a fast remodeling of synaptic ultrastructure at potentiated boutons : synaptic vesicles dispersed in the terminal and accumulated at the active zones, while active zone density and synaptic complexity increased. We suggest that these rapid and early structural rearrangements likely enable long-term increase in synaptic strength.

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Vesicle Clustering in a Living Synapse Depends on a Synapsin Region that Mediates Phase Separation

Abstract: Highlights d Reagents that bind to the IDR of synapsin cause dispersal of synaptic vesicle clusters d Inhibition of SH3 domain interactions with synapsin do not cause vesicle dispersal d Synaptic vesicle clustering in vivo can be explained by phase separation

Cited by 83 publications

References 48 publications

Recruitment of release sites underlies chemical presynaptic potentiation at hippocampal mossy fiber boutons

Recruitment of release sites underlies chemical presynaptic potentiation at hippocampal mossy fiber boutons

Axon terminals control endolysosome diffusion to support synaptic remodelling

Increased and synchronous recruitment of release sites underlies hippocampal mossy fiber presynaptic potentiation

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