PXD050719
PXD050719 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Actin-nucleation promoting factor N-WASP influences alpha-synuclein condensates and pathology |
Description | Abnormal intraneuronal accumulation of soluble and insoluble alpha-synuclein (alpha-Syn) is one of the main pathological hallmarks of synucleinopathies, such as Parkinson’s disease (PD). It has been well- documented that the reversible liquid-liquid phase separation of alpha-Syn can modulate synaptic vesicle condensates at the presynaptic terminals. However, alpha-Syn can also form liquid-like droplets that may convert into amyloid-enriched hydrogels or fibrillar polymorphs under stressful conditions. To advance our understanding on the mechanisms underlying alpha-Syn phase transition, we employed a series of unbiased proteomic analyses and found that actin and actin regulators are part of the alpha-Syn interactome. We focused on Neural Wiskott-Aldrich syndrome protein (N-WASP) because of its association with a rare early-onset familial form of PD. In cultured cells, we demonstrate that N-WASP undergoes phase separation and can be recruited to synapsin-1 liquid-like droplets, whereas it is excluded from alpha-Syn/synapsin-1 condensates. Consistently, we provide evidence that wsp-1/WASL loss of function (lof) alters the number and dynamics of alpha-Syn inclusions in the nematode Caenorhabditis elegans. Together, our findings indicate that N-WASP expression may create permissive conditions that promote alpha-Syn condensates and their potentially deleterious conversion into toxic species. |
HostingRepository | jPOST |
AnnounceDate | 2025-03-22 |
AnnouncementXML | Submission_2025-03-21_08:00:04.858.xml |
DigitalObjectIdentifier | |
ReviewLevel | Non peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Enzo Scifo |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Caenorhabditis elegans; NCBI TaxID: 6239; |
ModificationList | S-carboxamidomethyl-L-cysteine; N6-acetyl-L-lysine; alpha-amino acetylated residue; L-methionine sulfoxide |
Instrument | Orbitrap Exploris 480 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2024-03-18 04:48:46 | ID requested | |
⏵ 1 | 2025-03-21 08:00:05 | announced |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: alpha-synuclein |
Caenorhabditis elegans |
liquid-liquid phase separation |
Neural Wiskott-Aldrich syndrome protein (N-WASP) |
Contact List
Dr. Daniele Bano | |
---|---|
lab head | |
Enzo Scifo | |
contact affiliation | DZNE |
dataset submitter |
Full Dataset Link List
jPOST dataset URI |
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.jpostdb.org/JPST002992/ |