New Publication in Science Advances Congratulations to Dr. Sunayana Dagar and all team members on this outstanding achievement!

We are excited to share our latest publication:“Membrane-associated Rhes–SLC4A7 complex orchestrates tunneling nanotube formation and mutant Huntingtin spread,” now published in Science Advances.

In this study, we uncover a novel mechanism linking membrane signaling, intracellular pH regulation, and intercellular communication in Huntington disease. We identify SLC4A7 as a key membrane interactor of Rhes and demonstrate that this interaction regulates intracellular pH to drive tunneling nanotube (TNT) formation. Importantly, these TNTs facilitate the intercellular spread of mutant Huntingtin (mHTT), a central pathogenic event in disease progression.

Using pharmacological inhibition, siRNA knockdown, and genetic deletion approaches, we show that disrupting SLC4A7 significantly reduces pH changes, TNT formation, and mHTT transmission. These findings establish a Rhes–SLC4A7–pH axis as a critical driver of pathogenic protein spread and highlight a new therapeutic target in neurodegeneration.

https://video.wixstatic.com/video/629fa5_fc5fcf2d28404a32b4105902d4de9251/480p/mp4/file.mp4

Bicarbonate transporter SLC4A7 and Rhes protein helps shuttle mutant huntingtin (mHTT) between striatal neuronal cells via tunneling nanotubes (TNTs). Cargo exchange occurs within minutes, indicated by yellow or white arrowheads. Magenta = Rhes, Red = mutant huntingtin (mHTT), Green = SLC4A7

Full paper link:

https://www.science.org/doi/10.1126/sciadv.aea1226