2019
DOI: 10.1073/pnas.1903049116
|View full text |Cite
|
Sign up to set email alerts
|

Functional cooperation of α-synuclein and VAMP2 in synaptic vesicle recycling

Abstract: The function of α-synuclein (α-syn) has been long debated, and two seemingly divergent views have emerged. In one, α-syn binds to VAMP2, acting as a SNARE chaperone—but with no effect on neurotransmission—while another posits that α-syn attenuates neurotransmitter release by restricting synaptic vesicle mobilization and recycling. Here, we show that α-syn–VAMP2 interactions are necessary for α-syn–induced synaptic attenuation. Our data connect divergent views and suggest a unified model of α-syn function.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1
1

Citation Types

8
131
2

Year Published

2019
2019
2024
2024

Publication Types

Select...
8
1
1

Relationship

0
10

Authors

Journals

citations
Cited by 152 publications
(141 citation statements)
references
References 15 publications
8
131
2
Order By: Relevance
“…The enrichment of α-synuclein at the presynaptic terminal is the mostly likely reason for initiation of aggregate formation in the axon. Interaction of αsynuclein with partners such as VAMP2, CSPα, and synapsin may also enhance presynaptic enrichment of αsynuclein [108][109][110][111].…”
Section: Are Larger Filaments Fragmented and Released By The Neuron Amentioning
confidence: 99%
“…The enrichment of α-synuclein at the presynaptic terminal is the mostly likely reason for initiation of aggregate formation in the axon. Interaction of αsynuclein with partners such as VAMP2, CSPα, and synapsin may also enhance presynaptic enrichment of αsynuclein [108][109][110][111].…”
Section: Are Larger Filaments Fragmented and Released By The Neuron Amentioning
confidence: 99%
“…Alternatively, the effect on SNARE complexes may influence a property of the nerve terminal not evident from post‐synaptic recording, and this might secondarily affect SNARE complexes. Very recent work has provided additional evidence for an interaction of the α‐synuclein C‐terminus with VAMP2 and used mutations disrupting the interaction to implicate VAMP2 in the inhibition of synaptic vesicle exocytosis by over‐expressed synuclein (Sun et al ). Since VAMP2 is required for most transmitter release, it is however difficult to determine whether α‐synuclein can inhibit exocytosis in the absence of VAMP2.…”
Section: The Function Of α‐Synucleinmentioning
confidence: 99%
“…Further evidence linking α-synuclein and vesicular dynamics was demonstrated by Burré et al, 2010), when oligomeric α-synuclein was shown to promote snare complexes both in vivo and in vitro, however, it was shown to inhibit membrane fusion. Moreover, binding of calcium to the c-terminus of α-synuclein augmented its lipid-binding property (Lautenschlager et al, 2018) and additionally α-synuclein overexpression facilitated its interaction with VAMP2 and modulate exocytosis (Sun et al, 2019) but whether this occurs in normal physiology remains to be determined. In addition, using cryoelectron tomography, Vargas et al demonstrated that deletion of all three forms (α,β,γ) of synuclein increases synaptic vesicle (SV) tethering at the active zone but decreases the interlinking of SVs by short connectors (Vargas et al, 2017).…”
Section: Alpha-synuclein (α-Synuclein)mentioning
confidence: 99%