Sep 24, 2010 · Here, we show that maintenance of continuous presynaptic SNARE-complex assembly required a nonclassical chaperone activity mediated by synucleins. Specifically, α-synuclein directly bound to the SNARE-protein synaptobrevin-2/vesicle-associated membrane protein 2 (VAMP2) and promoted SNARE-complex assembly.

Jan 15, 2023 · Through its membrane-bound state, α-synuclein functions in neurotransmitter release by modulating several steps in the synaptic vesicle cycle, including synaptic vesicle clustering and docking, SNARE complex assembly, and homeostasis of synaptic vesicle pools.

Jan 15, 2023 · α-Synuclein is known to promote SNARE-complex assembly during vesicle docking and fusion steps. However, it misfolds into neurotoxic oligomeric species. α-Synuclein oligomers exert aberrant effects on presynaptic fusion machinery, thereby leading to neurodegeneration.

α-Synuclein, a protein implicated in neurodegeneration and cancer, is shown to bind to SNARE proteins, which mediate membrane fusion in synaptic transmission and cell growth, and to promote the assembly of SNARE proteins into SNARE-complexes during fusion.

In this review, I focus on the structural characteristics of α-synuclein, its cellular and subcellular localization, and discuss how this relates to its function in neurons, in particular at the neuronal synapse. Keywords: α-synuclein, synapse, membranes, SNARE, neurotransmitter release, synaptic vesicles.

Aug 28, 2014 · Our data delineate a folding pathway for α-synuclein that ranges from a monomeric unfolded form in cytosol to a physiologically functional multimeric form that is membrane bound and chaperones SNARE complex assembly, and that may protect against neurodegeneration.

Evidence suggests that alpha-synuclein functions as a molecular chaperone in the formation of SNARE complexes. [ 6 ] [ 7 ] In particular, it simultaneously binds to phospholipids of the plasma membrane via its N-terminus domain and to synaptobrevin -2 via its C-terminus domain, with increased importance during synaptic activity. [ 38 ]

May 26, 2021 · One of the potential toxicities of α-Syn oligomers is their inhibition of SNARE-mediated vesicle fusion by specifically interacting with vesicle-SNARE protein synaptobrevin-2 (Syb2), which...

Here we found that α-syn secretion is SNARE-dependent by systematically knocking down Q-SNAREs and R-SNAREs in exocytosis pathways. α-Syn secretion was mainly mediated by syntaxin 4 (STX4) and synaptosomal-associated protein 23 (SNAP23), but did not require STX1 and SNAP25, in differentiated SH-SY5Y cells.

Dec 23, 2022 · Here, we present an overview of the effects of α-synuclein on SNARE-complex assembly, neurotransmitter release, and synaptic vesicle pool homeostasis, and discuss how the observed divergent effects of α-synuclein on neurotransmitter release can be reconciled.