Separating receptor and ligand

Axonal pathfinding in motor neurons depends on surrounding guidance cues, including the membrane-bound ephrinA ligands, which repel growth cones that express EphA receptors. But many of those same growth cones also contain their own ephrinA. Now, Till Marquardt, Ryuichi Shirasaki, Samuel Pfaff, and colleagues (Salk Institute, La Jolla, CA) show how EphA ignores self-ephrinA during growth cone guidance.The authors find that ephrinA ligands that are on the same cell as a EphA receptor do not interfere with that receptor's ability to sense ligands on other cells. The interference is avoided by segregating receptor and ligand to different submembrane domains. EphrinA ligands, which are GPI-linked, colocalized with a lipid raft marker. EphA receptors, on the other hand, were found in nearby but distinct (presumably nonraft) domains. Forced mixing of the two, by expressing a transmembrane...