Membrane-associated Rhes-Slc4a7 complex orchestrates tunneling nanotube formation and mutant Huntingtin spread - PubMed
5 hours ago
- #Tunneling nanotubes
- #Huntington's disease
- #Rhes-Slc4a7 complex
- The study identifies the Rhes-Slc4a7 complex as crucial for tunneling nanotube (TNT) formation and mutant Huntingtin (mHTT) spread in Huntington's disease (HD).
- Slc4a7, an intracellular pH sensor, is a key membrane-binding partner of Rhes, influencing TNT formation and mHTT transfer.
- Depletion or inhibition of Slc4a7 reduces Rhes-induced TNT formation and suppresses mHTT intercellular transfer.
- Rhes interacts with Slc4a7 through its amino- and carboxyl-terminal domains, modulating intracellular pH to facilitate TNT formation, independent of Slc4a7's transporter activity.
- Inhibition of Rhes farnesylation disrupts its binding to Slc4a7 and abolishes TNT formation.
- Slc4a7 knock-out mice show reduced mHTT transmission in the striatum, highlighting Slc4a7 as a potential therapeutic target in HD.