PXD036727 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Altered plasma membrane abundance of the sulfatide-binding protein NF155 links glycosphingolipid imbalances to demyelination |
Description | Myelination of axons enables efficient signal propagation in neurones. Myelin is a multi-layered membrane that wraps around neuronal axons forming extremely tight contacts that insulate the axon. Tight contact between the axon and myelin sheath is mediated by specific plasma membrane proteins and lipids, with disruption to these contacts causing devastating demyelinating diseases. We have generated two cell-based models of demyelinating sphingolipidoses and shown that the altered lipid metabolism changes the plasma membrane protein composition. The proteins that are altered in these cells play roles in cell adhesion and signalling, several of which have previously been implicated in a range of neurological diseases. The adhesion molecule Neurofascin, with a known role in myelin-axon contact sites, is significantly altered in response to sphingolipid imbalances, highlighting a potential new player contributing to the pathogenesis of galactosphingolipid-mediated diseases. We show that the Neurofascin isoform NF155, but not NF186, directly binds the sphingolipid sulfatide, but does not bind other galactosylated-sphingolipids. Furthermore, this interaction requires the full-length extracellular domain of NF155 and that the structure of this domain adopts an S-shape with important implications for the arrangement of proteins in the tight axon-myelin space. Together, this work identifies that glycosphingolipid imbalances drive changes in membrane protein abundance and that this may be driven by direct interactions between extracellular portions of these proteins with specific lipid headgroups. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_05:44:40.959.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD036727 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | James Williamson |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-09-14 03:20:37 | ID requested | |
1 | 2023-04-06 02:55:01 | announced | |
2 | 2023-11-14 08:57:44 | announced | 2023-11-14: Updated project metadata. |
⏵ 3 | 2024-10-22 05:44:41 | announced | 2024-10-22: Updated project metadata. |
Publication List
Keyword List
submitter keyword: galactosylceramide, neurofascin, myelination, sulfatide,Krabbe Disease |
Contact List
Paul Lehner |
contact affiliation | Cambridge Institute of Therapeutic Immunology and Infectious Diseases, Department of Medicine, University of Cambridge, |
contact email | pjl30@cam.ac.uk |
lab head | |
James Williamson |
contact affiliation | University of Cambridge |
contact email | jcw76@cam.ac.uk |
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/2023/04/PXD036727 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD036727
- Label: PRIDE project
- Name: Altered plasma membrane abundance of the sulfatide-binding protein NF155 links glycosphingolipid imbalances to demyelination