Gingras Lab Develops Strategy for Identifying Protein Associations on the Cell Surface
By
Liliana Trajceska and Saya Sedighi
The Gingras Lab at the Lunenfeld-Tanenbaum Research Institute, part of Sinai Health, led by PhD candidate Rasha Al Mismar and principal investigator Dr. Anne-Claude Gingras, has introduced an innovative method to explore cell-surface protein interactions. Called extracellular TurboID (ecTurboID), this new technique offers a fast and precise way to study the “surfaceome” — the collection of proteins on the cell’s surface that play critical roles in signalling and are often implicated in diseases.
This innovative strategy, which enables the discovery of ligand-dependent protein interactions within short 15-minute windows, has been optimized for extracellular proteins, effectively capturing interactomes for numerous plasma membrane proteins.
Using ecTurboID, the team profiled several transmembrane proteins, including epidermal growth factor receptor (EGFR), identifying both novel and previously known interactions. Notably, EGF stimulation induced an association between EGFR and the low-density lipoprotein receptor (LDLR). This association is due to changes in LDLR's interactome and its increased proximity to proteins that regulate EGFR signalling. This finding highlights the utility of ecTurboID in uncovering dynamic extracellular associations between plasma membrane proteins.
When combined with existing cell surface profiling tools, ecTurboID has the potential to significantly advance research on diseases associated with the diverse range of proteins linked to the plasma membrane, referred to as the "surfaceome".
"We anticipate that ecTurboID will be valuable for investigating extracellular protein associations of diverse plasma membrane proteins, systematically and dynamically, which will provide transformative insights into cellular signal transduction in health and disease," said Al Mismar.
The research, featured on the cover of Science Signaling, shows that ecTurboID is a powerful new tool for studying the interactions between proteins on the surface of cells.
