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Synaptic vesicle binding of α-synuclein is modulated by β- and γ-synucleins.

TitleSynaptic vesicle binding of α-synuclein is modulated by β- and γ-synucleins.
Publication TypeJournal Article
Year of Publication2022
AuthorsCarnazza KE, Komer LE, Xie YXue, Pineda A, Briano JAntonio, Gao V, Na Y, Ramlall T, Buchman VL, Eliezer D, Sharma M, Burré J
JournalCell Rep
Volume39
Issue2
Pagination110675
Date Published2022 Apr 12
ISSN2211-1247
Keywordsalpha-Synuclein, Animals, beta-Synuclein, gamma-Synuclein, Mice, Presynaptic Terminals, Synaptic Vesicles
Abstract

α-synuclein, β-synuclein, and γ-synuclein are abundantly expressed proteins in the vertebrate nervous system. α-synuclein functions in neurotransmitter release by binding to and clustering synaptic vesicles and chaperoning SNARE-complex assembly. Pathologically, aggregates originating from soluble pools of α-synuclein are deposited into Lewy bodies in Parkinson's disease and related synucleinopathies. The functions of β-synuclein and γ-synuclein in presynaptic terminals remain poorly studied. Using in vitro liposome binding studies, circular dichroism spectroscopy, immunoprecipitation, and fluorescence resonance energy transfer (FRET) experiments on isolated synaptic vesicles in combination with subcellular fractionation of brains from synuclein mouse models, we show that β-synuclein and γ-synuclein have a reduced affinity toward synaptic vesicles compared with α-synuclein, and that heteromerization of β-synuclein or γ-synuclein with α-synuclein results in reduced synaptic vesicle binding of α-synuclein in a concentration-dependent manner. Our data suggest that β-synuclein and γ-synuclein are modulators of synaptic vesicle binding of α-synuclein and thereby reduce α-synuclein's physiological activity at the neuronal synapse.

DOI10.1016/j.celrep.2022.110675
Alternate JournalCell Rep
PubMed ID35417693