PXD027786

PXD027786 is an original dataset announced via ProteomeXchange.

Title	Beta-synuclein potentiates synaptic vesicle dopamine uptake and rescues dopaminergic neurons from MPTP-induced death in the absence of other synucleins
Description	Previous studies have demonstrated an importance of alpha-synuclein as a modulator of various mechanisms implicated in chemical neurotransmission but information about other two synuclein family members’ involvement in molecular processes taking place in presynaptic terminals is limited. Here we demonstrated that dopamine uptake by synaptic vesicles isolated from the striatum of mice lacking beta-synuclein was significantly reduced. Reciprocally, reintroduction, either in vivo or in vitro, of beta-synuclein but not alpha- or gamma-synuclein improved uptake by vesicles isolated from the striatum of triple alpha/beta/gamma-synuclein deficient mice. Proteomic analysis of synuclein-free and beta-synuclein-only-containing synaptic vesicles suggested that mechanistically, beta-synuclein potentiates vesicular monoamine transporter 2 (VMAT2)-dependent dopamine uptake by assembling specific multiprotein complexes comprised of resident vesicular proteins and transiently associated, predominantly cytosolic proteins. The increased availability of such complexes on the surface of striatal synaptic vesicles lacking other synucleins should also promote sequestration of 1-methyl-4-phenylpyridinium (MPP+), a toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which explains the resistance of dopaminergic neurons of substantia nigra lacking alpha-synuclein and/or gamma-synuclein to this neurotoxin.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-17_06:08:43.094.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD027786
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Arthur Kopylov
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	S-pyridylethyl-L-cysteine; monohydroxylated residue; deamidated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-06 03:45:28	ID requested
⏵ 1	2022-02-17 06:08:45	announced

Ninkina N, Millership SJ, Peters OM, Connor-Robson N, Chaprov K, Kopylov AT, Montoya A, Kramer H, Withers DJ, Buchman VL, -synuclein potentiates synaptic vesicle dopamine uptake and rescues dopaminergic neurons from MPTP-induced death in the absence of other synucleins. J Biol Chem, 297(6):101375(2021) [pubmed]

submitter keyword: synuclein, dopaminergic neurons, synapse, vesicles, transgenic mice, dopamine, MPTP toxicity, neurodegenerative disease, Parkinson’s disease, neurotransmitter vesicular uptake

Vladimir L. Buchman, Prof.
contact affiliation	School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, United Kingdom
contact email	buchmanvl@cf.ac.uk
lab head
Arthur Kopylov
contact affiliation	Institute of Biomedical Chemistry
contact email	a.t.kopylov@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD027786

PRIDE project URI

• PRIDE
  1. PXD027786
     1. Label: PRIDE project
     2. Name: Beta-synuclein potentiates synaptic vesicle dopamine uptake and rescues dopaminergic neurons from MPTP-induced death in the absence of other synucleins