PXD040141 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Dopamine transporter and synaptic vesicle sorting defects underlie auxilin-associated Parkinson’s disease |
Description | Auxilin participates in the uncoating of clathrin-coated vesicles (CCVs), thereby facilitating synaptic vesicle (SV) regeneration at presynaptic sites. Auxilin (DNAJC6/PARK19) loss-of-function mutations cause early-onset Parkinson’s disease (PD). Here, we utilized auxilin-knockout (KO) mice to elucidate the mechanisms through which auxilin deficiency and clathrin-uncoating deficits lead to PD. Auxilin KO mice display cardinal features of PD, including progressive motor deficits, α-synuclein pathology, nigral dopaminergic loss, and neuroinflammation. Significantly, treatment with L-DOPA ameliorated motor deficits. Unbiased proteomic and neurochemical analyses of auxilin KO brains indicated dopamine dys-homeostasis. We validated these findings by demonstrating slower dopamine reuptake kinetics in vivo, an effect associated with dopamine transporter misrouting into axonal membrane deformities in the dorsal striatum. Defective SV protein sorting and elevated synaptic autophagy also contribute to ineffective dopamine sequestration and compartmentalization, ultimately leading to neurodegeneration. This study advances our knowledge of how presynaptic endocytosis deficits lead to dopaminergic vulnerability and pathogenesis of PD. |
HostingRepository | PRIDE |
AnnounceDate | 2023-02-16 |
AnnouncementXML | Submission_2023-02-16_08:23:42.265.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | TuKietLam |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive Plus |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-02-16 03:45:16 | ID requested | |
⏵ 1 | 2023-02-16 08:23:42 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Dorsal striatum, Substantia nigra, Endolysosomal system, Dopamine, α-Synuclein, Clathrin coated vesicles, Synaptic autophagy,Clathrin mediated endocytosis, Axonal deformity, Lewy bodies, L-DOPA |
Contact List
TuKietLam |
contact affiliation | Keck MS & Proteomics Resource Yale School of Medicine |
contact email | tukiet.lam@yale.edu |
lab head | |
TuKietLam |
contact affiliation | Yale University |
contact email | tukiet.lam@yale.edu |
dataset submitter | |
Full Dataset Link List
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/2023/02/PXD040141 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD040141
- Label: PRIDE project
- Name: Dopamine transporter and synaptic vesicle sorting defects underlie auxilin-associated Parkinson’s disease