Synaptic Vesicle Endocytosis Impaired by Disruption of Dynamin-SH3 Domain Interactions

Shupliakov, Oleg; Lőw, Péter; Grabs, Detlev; Gad, Helge; Chen, Hong; David, Carol; Takei, Kohji; Camilli, Pietro De; Brodin, Lennart

doi:10.1126/science.276.5310.259

Cited by 456 publications

(466 citation statements)

References 27 publications

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“…Under low frequency APe stimulation matching splanchnic firing under basal sympathetic tone (0.5 Hz) [39][40][41], we show that transfection with a peptide fragment of the Dynamin I prolinerich domain (PRD) that competitively competes for binding to amphiphysin [17] has the result of blocking granule endocytosis. Consistent with previous work [4,19,25], disrupting clathrinmediated endocytosis by blocking synaptojanin/endophilin binding has no effect on membrane retrieval in these conditions.…”

Section: Discussionmentioning

confidence: 94%

“…The Dyn peptide ( figure 1A) was synthesized by Elim Biopharmaceuticals (Hayward, CA) after a previously-published sequence [17] and the PP-19 peptide ( figure 1A) was synthesised by Sigma Genosys (The Woodlands, TX, USA) after a previously published sequence [18]. Cells were transfected by using the Chariot (Active Motif, Carlsbad, CA) transfection method.…”

Section: Peptide Transfectionmentioning

confidence: 99%

“…We acutely transfected cells with a small synthetic peptide (Dyn) that contains the SH3 binding site. The Dyn peptide has been well characterized by several groups in multiple preparations and has been shown to specifically disrupt dynamin I(aa) binding to amphiphysin, which blocks endosomal scission and internalization [17,27]. We also took advantage of this peptide transfection technique to disrupt a key component in clathrin-mediated endocytosis.…”

Section: Membrane Trafficking Exhibits Differential Activity-dependenmentioning

confidence: 99%

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Dynamin I plays dual roles in the activity-dependent shift in exocytic mode in mouse adrenal chromaffin cells

Fulop

Doreian

Smith

2008

Archives of Biochemistry and Biophysics

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Under low stimulation, adrenal chromaffin cells release freely-soluble catecholamines through a restricted granule fusion pore while retaining the large neuropeptide-containing proteinacious granule core. Elevated activity causes dilation of the pore and release of all granule contents. Thus, physiological differential transmitter release is achieved through regulation of fusion pore dilation. We examined the mechanism for pore dilation utilizing a combined approach of peptide transfection, electrophysiology, electrochemistry and quantitative imaging techniques. We report that disruption of dynamin I function alters both fusion modes. Under low stimulation, interference with dynamin I does not affect granule fusion but blocks its re-internalization. In full collapse mode, disruption of dynamin I limits fusion pore dilation, but does not block membrane re-internalization. These data suggest that dynamin I is involved in both modes of exocytosis by regulating contraction or dilation of the fusion pore and thus contributes to activity-dependent differential transmitter release from the adrenal medulla.

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Section: Discussionmentioning

confidence: 94%

Section: Peptide Transfectionmentioning

confidence: 99%

Section: Membrane Trafficking Exhibits Differential Activity-dependenmentioning

confidence: 99%

See 1 more Smart Citation

Dynamin I plays dual roles in the activity-dependent shift in exocytic mode in mouse adrenal chromaffin cells

Fulop

Doreian

Smith

2008

Archives of Biochemistry and Biophysics

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“…A crucial part in synaptic vesicle endocytosis is played by the GTPase dynamin (FIG. 2), a mechanochemical enzyme recruited to endocytic sites by interaction with SH3 domain proteins 58,59 , including intersectin [60][61][62] , amphiphysin 63 , endophilin 64,65 and syndapin 66 , suggesting a tight interplay between BAR-SH3 protein-mediated membrane deformation (FIG. 2) and dynamin-catalyzed fission 58,67 .…”

Section: Box 1 | Presynaptic Organization -Exocytic and Endocytic Zonesmentioning

confidence: 99%

“…Such 'compensatory' endocytosis is indeed observed in neurons, although in most other cell types and systems endocytosis seems to be a constitutive process. Synaptic vesicle reformation at the nerve terminal is strongly activity-dependent, resulting in spatiotemporal coupling to the exocytic fusion of synaptic vesicle membranes 6,8,63,74 . under conditions of low-level synaptic activity, endocytic intermediates -for example, clathrin-coated structures undergoing fission -have been observed close to the release site as well as at more distant, lateral sites 74,75 .…”

Section: Box 1 | Presynaptic Organization -Exocytic and Endocytic Zonesmentioning

confidence: 99%

Protein scaffolds in the coupling of synaptic exocytosis and endocytosis

2011

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Communication between nerve cells largely occurs at chemical synapses -specialized sites of cell-cell contact where electrical signals trigger the exocytic release of neurotransmitter, which in turn activates postsynaptic receptor channels. The efficacy with which such chemical signals are transmitted is crucial for the functioning of the nervous system. Modulation of neurotransmission enables nerve cells to respond to a vast range of stimulus patterns. Synaptic activity can also be tremendously diverse; from the fast synapses of the hippocampus, to slow neuropeptide-containing synapses. Indeed, some signalling pathways are active in the absence of stimulation, such as those involved in the processing of sensory information, which transmit tonically at high rates of up to 100 Hz or more 1,2 .Intriguing questions arise from these facts, including how high rates of neurotransmission can be maintained over long periods of time, and what limits the ability of a given synapse to release neurotransmitter during sustained periods of activity. Recent data indicate that in many synapses, exocytosis of neurotransmitter is coupled to endocytosis, and that synapses have evolved a specialized apparatus of scaffolding proteins to comply with these demands. Such scaffolds aid the temporal and spatial coupling of exocytosis and endocytosis, and are crucial for maintaining rapid neurotransmission during sustained activity 3 .Exocytosis of neurotransmitter is triggered by stimulusinduced calcium influx into the nerve terminal 4,5 and the subsequent fusion of synaptic vesicles with the presynaptic plasma membrane at specialized regions called active zones (BOX 1). Exocytosed synaptic vesicle membrane proteins and lipids in turn are recycled at the endocytic or periactive zone (BOX 1) that surrounds the release site, to restore functional synaptic vesicle pools for reuse and to ensure long-term functionality of the synapse 6-8 (FIG. 1). Depending on the type of synapse and the stimulation frequency, several modes of endocytosis with different time constants -for example, fast and slow endocytosisseem to operate 7,9,10 . Clathrin-mediated endocytosis arguably represents the main pathway of synaptic vesicle endocytosis 6,8,11 , although other modes -for example, fast kiss-and-run exocytosis and endocytosis -could operate in parallel.Although the machineries for exocytic membrane fusion 12,13 and for endocytic retrieval of synaptic vesicle membranes have been studied separately in some detail 6,14 , comparatively little is known about the coupling between exocytosis and endocytosis. Here we synthesize recent data from physiological, morphological and biochemical studies in several model systems into hypothetical models for scaffold-based mechanisms underlying exocytic-endocytic coupling.The synaptic vesicle cycle Synaptic vesicle pools. Some defining features of chemical synapses are the presence of one or several clusters of synaptic vesicles in the presynaptic nerve terminal, and ultrastructural specializations at the pre-and postsy...

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Critical assessment of the involvement of perforations, spinules, and spine branching in hippocampal synapse formation

1998

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Several studies propose that long-term enhancement of synaptic transmission between neurons results from the enlargement, perforation, and splitting of synapses and dendritic spines. Unbiased analyses through serial electron microscopy were used to assess the morphological basis for synapse spilitting in hippocampal area CA1. Few perforated synapses and almost no split (i.e., branched) spines occurred at postnatal day 15, an age of high synaptogenesis; thus, synapse splitting is unlikely to be important during development. The synapse splitting hypothesis predicts an intermediate stage of branched spines with both heads sharing the same presynaptic bouton. Ninety-one branched dendritic spines were traced through serial sections, and the different branches never synapsed with the same presynaptic bouton. Projections from spines, called "spinules," have been thought to extend from perforations in the postsynaptic density (PSD), thereby dividing the presynaptic bouton. Forty-six spinules were traced, and only 13% emerged from perforations in the PSD. Most spinules emerged from the edges of nonperforated PSDs, or from spine necks, where they extended into boutons that were not presynaptic to the spine. In summary, these morphological characteristics are inconsistent with synapse and spine splitting. An alternative is discussed whereby perforated synapses and spinules are transient components of synaptic activation, and branched spines appear from synapses forming in close proximity to one another.

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Synaptic Vesicle Endocytosis Impaired by Disruption of Dynamin-SH3 Domain Interactions

Cited by 456 publications

References 27 publications

Dynamin I plays dual roles in the activity-dependent shift in exocytic mode in mouse adrenal chromaffin cells

Dynamin I plays dual roles in the activity-dependent shift in exocytic mode in mouse adrenal chromaffin cells

Protein scaffolds in the coupling of synaptic exocytosis and endocytosis

Critical assessment of the involvement of perforations, spinules, and spine branching in hippocampal synapse formation

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