⮝ Full datasets listing
PXD065528
PXD065528 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Membrane-Associated Rhes Slc4a7 Complex Orchestrates Tunneling Nanotube Formation and Mutant Huntingtin Spread |
| Description | Tunneling nanotubes are membranous structures that mediate intercellular transfer of proteins, including the pathogenic mutant Huntingtin protein in Huntingtons disease. We previously identified the ras homolog enriched in the striatum (Rhes) as a key regulator of TNT formation and mHTT transmission however, the molecular components underlying this process remained unknown. Here, using unbiased Liquid chromatography tandem mass spectrometry LC MSMS analysis of membrane associated Rhes complexes, we identify Slc4a7 (Solute Carrier Family 4 Member 7), an intracellular pH sensor, as a top membrane binding partner of Rhes. Functional studies revealed that siRNA mediated depletion or pharmacological inhibition of Slc4a7 significantly reduced Rhes induced TNT formation and suppressed mHTT intercellular transfer. Mechanistically, Rhes directly interacts with Slc4a7 through both its N and C terminal domains and modulates intracellular pH to facilitate TNT formation. This interaction does not depend on the transporter activity of Slc4a7. However, inhibition of Rhes farnesylation a lipid modification that anchors Rhes to the membrane disrupts its binding to Slc4a7 and abolishes TNT formation. Importantly, Slc4a7 knockout mice showed markedly reduced cell to cell transmission of mHTT in the striatum in vivo. Together, these findings uncover a previously unrecognized Rhes Slc4a7 signaling axis critical for TNT mediated mHTT transmission and highlight Slc4a7 as a potential therapeutic target to limit disease spread in HD. |
| HostingRepository | MassIVE |
| AnnounceDate | 2025-11-10 |
| AnnouncementXML | Submission_2025-11-10_09:32:16.825.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Gogce Ceren Crynen |
| SpeciesList | scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090; |
| ModificationList | Acetyl |
| Instrument | Orbitrap Fusion ETD |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-06-26 11:31:14 | ID requested | |
| ⏵ 1 | 2025-11-10 09:32:17 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: rhes, SLC4A7, Huntington disease, Neurodegeneration, protein protein interaction, tunneling nanotubes, DatasetType:Proteomics |
Contact List
| Srinivasa Subramaniam | |
|---|---|
| contact affiliation | Florida Atlantic University (FAU), Stiles-Nicholson Brain Institute |
| contact email | ssubramaniam@fau.edu |
| lab head | |
| Gogce Ceren Crynen | |
| contact affiliation | UF Scripps Biomedical Research |
| contact email | gogce@ufl.edu |
| dataset submitter | |
Full Dataset Link List
| MassIVE 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://massive-ftp.ucsd.edu/v10/MSV000098338/ |
